Analysis of the Causes and Phenotypic Variations of Acute flaccid paralysis with and without myelitis in a Pediatric Hospital Setting in Taiwan

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This study investigates the demographic and clinical characteristics, laboratory findings, and underlying causes of AFP in patients with and without myelitis (M-AFP and NM-AFP, respectively). Methods: Data were retrospectively collected from 39 patients diagnosed between 2012 and 2021, divided into M-AFP (n=22) and NM-AFP (n=17) groups. Patients with myelitis were identified via clinical symptoms and magnetic resonance imaging findings, while those without myelitis were diagnosed through clinical presentation and various diagnostic tools. Key demographic data, clinical characteristics, and laboratory results, such as cerebrospinal fluid white blood cell count and protein levels, were analyzed. Results: The study identified distinct etiologies for M-AFP, including multiple sclerosis, herpes simplex virus, and enterovirus, among others. In contrast, NM-AFP was associated with conditions such as polymyositis, Guillain-Barre syndrome, and hypokalemic periodic paralysis. Statistical analysis revealed significant differences in symptoms at onset, with limb numbness more prevalent in M-AFP and myalgia more common in NM-AFP. Although cerebrospinal fluid white blood cell counts were higher in M-AFP, the difference was not statistically significant. Conclusions: This comprehensive analysis highlights the diverse etiologies and clinical presentations of AFP, emphasizing the need for tailored diagnostic strategies to enhance patient care and outcomes. Acute flaccid paralysis myelitis children Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Acute flaccid paralysis (AFP) is a clinical syndrome characterized by the rapid onset of weakness or paralysis with reduced muscle tone in the absence of other obvious causes, such as trauma [ 1 ]. It represents a critical medical emergency due to its potential to progress rapidly and cause significant morbidity and mortality. The spectrum of conditions presenting with AFP is broad, encompassing various infectious, inflammatory, autoimmune, and metabolic etiologies [ 2 , 3 ]. Among these, myelitis, an inflammatory condition affecting the spinal cord, is a significant cause of AFP. Myelitis can result from a variety of underlying causes, including viral infections, autoimmune diseases, and demyelinating disorders [ 4 ]. However, AFP can also occur without myelitis, where the underlying etiologies are diverse and can include neuromuscular junction disorders, peripheral neuropathies, metabolic disturbances, and even hematologic malignancies. Conditions such as Guillain-Barre syndrome (GBS), polymyositis (PM), and hypokalemic periodic paralysis (hypoPP) are notable examples that must be considered in the differential diagnosis [ 5 , 6 ]. The diagnostic challenge is to accurately identify the underlying cause of AFP to initiate appropriate treatment promptly. Understanding the demographic and clinical characteristics of patients with AFP, along with detailed analysis of laboratory findings and identified causes, can significantly enhance diagnostic accuracy and patient outcomes. Previous studies have primarily focused on either AFP with myelitis or specific conditions within the NM-AFP, but comprehensive comparisons between these two categories remain limited. This study aims to fill this gap by providing a comparative analysis of AFP with and without myelitis, focusing on demographic data, clinical presentations, laboratory findings, and underlying causes. By delineating the distinct profiles of these two groups, we seek to improve the diagnostic approach and clinical management of AFP. The ultimate goal is to ensure that patients receive timely and appropriate interventions, reducing the risk of long-term complications and enhancing overall prognosis. 2. Material and Methods This study analyzed the demographic and clinical characteristics of patients with AFP with and without myelitis. Data were collected from medical records of patients diagnosed between 2012 and 2021. The study included a total of 39 patients, divided into two groups: those with myelitis (M-AFP, n=22) and those without myelitis (NM-AFP, n=17). 2.1 Study Population: Participants were categorized based on the presence or absence of myelitis. Patients with myelitis were identified through clinical symptoms and confirmed by MRI findings, while those without myelitis were diagnosed based on clinical presentation and other diagnostic tools. 2.2 Ethical Approval and Data Collection: This study received approval from the Institutional Review Board of China Medical University Children’s Hospital (# DMR-113-041/CMUH113-REC2-029). In this retrospective cohort study, we aimed to explore the demographic and clinical characteristics of patients with acute flaccid paralysis, as well as their underlying causes and their approaches to diagnosis. We have adopted a medical record screening strategy and used a big data system to target the pediatric patients who came to our hospital for medical treatment in the past 10 years (Between January 1, 2012 and December 31, 2021). The keywords in their chief medical complaints are: (1) Limb or muscle weakness (2) Limb or muscle hemiplegia (3) Immobility (4) Limb pain (5) Feeling of "paralysis" or "numbness". Conduct in-depth comparison based on the keywords (1)-(5) to obtain 14,500 pieces of information, and further screen patients who meet the conditions of this study (Figure 1). Additionally, demographic data, including sex and age of onset, were recorded. Clinical characteristics, such as symptoms at onset, season of onset, and history of illness within two months prior to onset, were documented. Laboratory results, including cerebrospinal fluid (CSF), white blood cell count (WBC) and protein levels, were also collected. 2.3 Exclusion Criteria: Exclusions were made for patients who either: 2.3.1 Children who meet the definition of Benign acute childhood myositis (BACM) [7]. BACM is a self-limiting inflammatory muscle condition that primarily affects children. The condition tends to present itself during or shortly after a viral illness. Key features of BACM include: 2.3.1.1 Muscle Pain: Typically severe and localized to the calves, causing difficulty in walking. 2.3.1.2 Age Group: Most commonly affects school-aged children. 2.3.1.3 Viral Association: Often follows an upper respiratory tract infection or influenza. 2.3.1.4 Duration: Symptoms generally resolve within a few days to a week without specific treatment. 2.3.1.5 Laboratory Findings: Elevated serum creatine kinase levels are often observed, indicating muscle damage. 2.3.1.6 Clinical Course: BACM is considered benign and does not lead to long-term muscle complications. 2.3.2 Muscle or limb pain due to trauma of any cause (e.g., fractures, sprains, and contusions) 2.3.3 Temporary limb weakness caused by acute metabolic or neurological events (e.g., Todd's paralysis, hypoglycemia). 2.3.4 Cachexia caused by major diseases (e.g., malignant tumors, immune deficiency). 2.3.5 "Reluctance to move" caused by psychological or mental factors (e.g., somatosensory mental illness or chronic fatigue syndrome, depression, and conversion disorder). 2.3.6 Others whose diagnosis cannot be established. 2.4 Statistical Analysis: Descriptive statistics were used to summarize the demographic and clinical characteristics of the two groups. Continuous variables were reported as mean ± standard deviation, and categorical variables were presented as frequencies and percentages. The chi-square test or Fisher's exact test was used to compare categorical variables, while the independent t-test was used for continuous variables. A p-value of less than 0.05 was considered statistically significant. 2.5 Identification of Causes: For patients with myelitis, the underlying causes were identified using MRI (typically T2-weighted imaging combined with contrast-enhanced T1-weighted imaging and Short Tau Inversion Recovery, STIR) and other diagnostic tools. Similarly, the causes of AFP in patients without myelitis were determined using various diagnostic methods, including imaging studies, laboratory tests, and clinical criteria. In addition, differences in symptoms between individual patients were analyzed through medical records, and differences in causes, demographics, clinical manifestations, and diagnostic patterns of the two types of patients were investigated. 3. Results 3.1 Demographic and Clinical Characteristics: The demographic and clinical characteristics of the study population are summarized in Table 1. The mean age of onset for M-AFP was 10.5 ± 8.7 years, and for NM-AFP, it was 10.6 ± 4.9 years (p = 0.96). There was no significant difference in sex distribution between the two groups (p = 0.85). The distribution of onset by season did not show a significant difference between M-AFP and NM-AFP (p > 0.05 for all comparisons).All patients with myelitis presented with limb weakness (100%), compared to 16 patients (94%) in NM-AFP (p = 0.99). Limb numbness was significantly more common in M-AFP (91% vs. 29%, p < 0.001), whereas myalgia was more prevalent in NM-AFP (88% vs. 23%, p < 0.001). The mean CSF WBC count was higher in M-AFP (52.4 ± 62.7 cells/μL) compared to NM-AFP (27.6 ± 50.2 cells/μL), but this difference was not statistically significant (p = 0.22). The mean CSF protein levels were similar between the two groups (61.8 ± 40.9 mg/dL vs. 68.1 ± 47.6 mg/dL, p = 0.65). 3.2 Underlying Causes: Tables 2 and 3 present the identified causes of acute myelitis and AFP without myelitis, respectively. In M-AFP, the causes included multiple sclerosis, herpes simplex virus, Behcet's disease, enterovirus, systemic lupus erythematosus, influenza A, spinal subdural hematoma, and Enterovirus D68. In NM-AFP, the causes included polymyositis, porphyria, juvenile dermatomyositis, myasthenia gravis, neuroblastoma, acute lymphoblastic leukemia (ALL), GBS, spinal cord injury, and hypoPP 3.3 Hospitalization Days and Diagnosis Time: Figure 2 presents box plots comparing the number of hospitalization days and diagnosis time between the two groups: 3.3.1 Hospitalization Days: In NM-AFP, the median number of hospitalization days was approximately 8 days, with an interquartile range (IQR) of about 3 to 15 days, including outliers extending up to 105 days. In contrast, M-AFP had a median of roughly 11 days, an IQR of about 7 to 15 days, and outliers reaching up to 85 days. The p-value of 0.714 indicates no statistically significant difference between the two groups regarding hospitalization days. 3.3.2 Diagnosis Time: NM-AFP had a median diagnosis time of around 22 days, with an IQR spanning from about 7 to 65 days, and outliers extending up to 150 days. M-AFP showed a much faster median diagnosis time of approximately 7 days, an IQR of about 2 to 12 days, and outliers reaching up to 130 days. The p-value of 0.818 suggests no statistically significant difference between the groups concerning diagnosis time. 3.4 Statistical Significance of Underlying Causes: The prevalence of other identified causes of infection was significantly higher in M-AFP (36% vs. 0%, p = 0.005). Similarly, the identification of underlying causes for diseases was significantly higher in NM-AFP (94% vs. 59%, p = 0.013). 4 Discussion This study provides a comprehensive analysis of the demographic and clinical characteristics, symptoms, laboratory results, and underlying causes of M-AFP and NM-AFP. The findings underscore significant clinical differences between these two groups, offering valuable insights for clinical practice and further research. 4.1 Demographic and Clinical Characteristics: The demographic data revealed no significant difference in the mean age of onset or sex distribution between patients with and without myelitis. Despite no previous research directly comparing demographic data of M-AFP and NM-AFP, studies focused on Guillain-Barré syndrome [8] and AFP of unknown etiology [9] indicate that AFP can affect individuals of any age and gender, highlighting its non-discriminatory nature. Understanding these demographic characteristics is crucial as it broadens the differential diagnosis in clinical settings, ensuring that clinicians consider a wide range of potential underlying conditions when diagnosing AFP. A notable finding is the significant difference in initial symptoms between M-AFP and NM-AFP. Patients with myelitis frequently presented with limb weakness and numbness, symptoms commonly associated with the inflammation and damage to the spinal cord characteristic of myelitis [10-12]. This is contrasted by NM-AFP, which reported higher instances of myalgia, characteristic of idiopathic inflammatory myopathies such as polymyositis and juvenile dermatomyositis [13,14]. This differentiation in symptoms guides clinicians towards the appropriate diagnostic pathway and helps prioritize investigations that can confirm the underlying cause. 4.2 Laboratory Results: Analysis of CSF showed higher mean WBC counts in M-AFP compared to NM-AFP, although the difference was not statistically significant. Elevated CSF WBC counts in myelitis patients can indicate an inflammatory or infectious process within the CNS [15]. While the study did not find significant differences in CSF protein levels between M-AFP and NM-AFP, elevated protein levels remain a critical marker in diagnosing CNS pathologies [16,17]. 4.3 Underlying Causes: The etiology of AFP in our cohort was diverse. In M-AFP, conditions such as multiple sclerosis, herpes simplex virus, Behcet’s disease, systemic lupus erythematosus, influenza A, spinal subdural hematoma, enterovirus-D68, and enterovirus A71 were identified (Figure 3) [16,18-20]. This wide spectrum of infectious, inflammatory, and autoimmune conditions leading to myelitis underscores the need for comprehensive diagnostic approaches, including MRI and specific laboratory tests (e.g., CSF analysis, viral PCR tests, autoimmune markers, and other blood tests) to accurately identify the underlying cause. Conversely, NM-AFP presented a broader array of underlying causes, highlighting the heterogeneity of this patient group. Conditions such as PM, porphyria, JDM, myasthenia gravis, neuroblastoma, ALL, GBS, spinal cord injury, and hypoPP were identified [21-24]. The variety of these conditions indicates that clinicians must maintain a high index of suspicion for a wide range of potential etiologies, including hematology and oncology diseases like ALL and neuroblastoma [25,26]. This is crucial because hematologic disorders can present with neurological manifestations that may initially be misinterpreted as primary neurological conditions. 4.4 Clinical Significance of Hematologic Disorders: Examples of ALL and Neuroblastoma: Hematologic disorders, such as neuroblastoma and ALL, are particularly noteworthy due to their potential to cause significant morbidity and mortality if not promptly diagnosed and treated. ALL can present with various neurological manifestations, such as headaches, seizures, and focal neurological deficits, due to leukemic infiltration, treatment-related neurotoxicity, or secondary infections. These symptoms can mimic other neurological conditions and lead to an initial misdiagnosis as a primary neurological disorder rather than a hematologic malignancy [27]. Nonetheless, the presentation of AFP in ALL can often be subtle, requiring a high index of suspicion. Neuroblastoma is a malignant tumor arising from neural crest cells, typically affecting young children. It can lead to AFP through various mechanisms, including direct compression of the spinal cord or nerve roots, paraneoplastic syndromes (e.g., opsoclonus-myoclonus syndrome), and infiltration of the spinal canal (Figure 4) [28]. This tumor's diverse presentations often include acute weakness or paralysis, sometimes leading to initial misdiagnosis as a primary neurological disorder [29]. By using neuroblastoma and ALL as examples, we underscore the importance of considering hematologic disorders in the differential diagnosis of AFP. This approach ensures that clinicians can identify and manage these potentially life-threatening conditions effectively, improving patient outcomes. 4.5 Diagnostic Tools for NM-AFP: Given the diverse underlying causes in NM-AFP, a broad range of diagnostic tools must be considered. For instance, neuroimaging, such as MRI, is essential for detecting structural abnormalities, including tumors and spinal cord injuries (Figure 5A) . Muscle biopsy and serological tests for muscle-specific antibodies are crucial for diagnosing conditions like PM and JDM [30,31]. Electromyography, nerve conduction studies, spinal MRI and CSF-Immunofixation electrophoresis are vital for diagnosing peripheral neuropathies such as GBS ( Figure 5B-D ) and porphyria [32,33]. In cases of suspected hematologic disorders, initial laboratory tests such as a complete blood count and peripheral blood smear can provide crucial clues. Further confirmation through bone marrow biopsy and flow cytometry is often required to diagnose conditions like ALL [34]. For hypoPP, a detailed history and blood tests during an episode of paralysis are essential to confirm the diagnosis [35]. 4.6 Limitations: This study has several limitations. The relatively small sample size may limit the generalizability of the findings. Additionally, the retrospective nature of the study and reliance on medical records may introduce selection bias and inaccuracies in data recording. Furthermore, because software was used to assist in screening a large number of case data over the past 10 years using keywords instead of manual screening, the number of subjects included and excluded in the experiment is very likely to be different from the actual number of patients. Future prospective studies with larger sample sizes are needed to validate these findings and further explore the differences between AFP with and without myelitis. 5 Conclusion This study provides a detailed comparative analysis of AFP with and without myelitis, highlighting significant differences in clinical presentation, laboratory findings, and underlying causes. Patients with myelitis (M-AFP) frequently presented with limb numbness and had higher cerebrospinal fluid white blood cell counts, though the latter was not statistically significant. In contrast, patients without myelitis (NM-AFP) commonly experienced myalgia and had a broader array of underlying conditions, including polymyositis, Guillain-Barre syndrome, and various hematologic disorders. These findings emphasize the importance of a tailored diagnostic approach to enhance the accuracy of diagnosis and the timeliness of interventions. While the study's retrospective nature and small sample size are limitations, the insights gained underscore the need for comprehensive diagnostic strategies to manage AFP effectively. Future research should focus on larger, prospective studies to validate these findings and further refine clinical management protocols, ultimately aiming to improve patient outcomes and reduce the risk of long-term complications. Abbreviations AChR-Ab: Acetylcholine Receptor Antibodies AFP: Acute Flaccid Paralysis ALL: Acute Lymphoblastic Leukemia BACM: Benign Acute Childhood Myositis CNS: Central Nervous System CSF: Cerebrospinal Fluid CT: Computed Tomography DTR: Deep Tendon Reflexes EV: Enterovirus EV-D68: Enterovirus D68 F-18 FDG: Fluorodeoxyglucose (F-18) GBS: Guillain-Barre Syndrome hypoPP: Hypokalemic Periodic Paralysis IQR: Interquartile Range JDM: Juvenile Dermatomyositis MG: Myasthenia Gravis MRI: Magnetic Resonance Imaging MS: Multiple Sclerosis NM-AFP: Acute Flaccid Paralysis without Myelitis PCR: Polymerase Chain Reaction PET: Positron Emission Tomography PM: Polymyositis SLE: Systemic Lupus Erythematosus STIR: Short Tau Inversion Recovery T2W: T2-Weighted WBC: White Blood Cell Declarations Acknowledgements On behalf of all the authors (the names are as follows: SYH, RHF, YTC, ICC and CHL), we extend our utmost gratitude to the medical and financial support of China Medical University Hospital and China Medical University Children’s Hospital (DMR-113-041/CMUH113-REC2-029) to the completion of this article. We express our sincere appreciation to the Department of Imaging Medicine at China Medical University Hospital. Their invaluable insights and timely guidance have been instrumental in resolving intricate diagnostic cases and facilitating the interpretation of medical images. It is unequivocally due to their invaluable assistance that this article has reached its successful culmination. Author contributions SYH provided treatment to the patient, collected the data and wrote the draft. RHF and YTC participated in the design of the study and wrote the manuscript. ICC and CHL provided their experience for the patient’ s collection and modified the manuscript accordingly. All authors read and approved the final manuscript. Funding Not applicable. Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Declarations Ethics approval and consent to participate: Consent for discussion of the clinical history was provided by the medical records. The study protocol was approved by the Ethics Review Board of the China Medical University ethics committee (Approval # DMR-113-041/CMUH113-REC2-029). Written informed consent of participation was obtained from the legal guardians. A statement to confirm that all methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication The patient’s guardians have consented to submission of this study to the journal, and we have obtained a written informed consent. Competing interests The authors declare that they have no competing interests. References Hosoya M. Brain Nerve. 2022;74(10):1153–62. 10.11477/mf.1416202203 . Theroux LM, Brenton JN. Acute Transverse and Flaccid Myelitis in Children. 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Published 2012 Mar 15. 10.1136/bmj.e1181 Lacomis D. Making the Diagnosis of Myositis: Muscle Biopsy and Interpretation. In: Aggarwal R, Oddis C, editors. Managing Myositis. Cham: Springer; 2020. https://doi.org/10.1007/978-3-030-15820-0_13 . Lin CS, Krishnan AV, Lee MJ, et al. Nerve function and dysfunction in acute intermittent porphyria. Brain. 2008;131(Pt 9):2510–9. 10.1093/brain/awn152 . Alayafi HA, Aljumah TK, Alluhayyan OB, Alqaraishi A, Aljwair SA. Acute Intermittent Porphyria Labeled Initially As Guillain-Barre Syndrome: Challenging Diagnosis. Cureus. 2023;15(11):e48753. 10.7759/cureus.48753 . Published 2023 Nov 13. Harvey RC, Tasian SK. Clinical diagnostics and treatment strategies for Philadelphia chromosome-like acute lymphoblastic leukemia. Blood Adv. 2020;4(1):218–28. 10.1182/bloodadvances.2019000163 . Lin YF, Wu CC, Pei D, Chu SJ, Lin SH. Diagnosing thyrotoxic periodic paralysis in the ED. Am J Emerg Med. 2003;21(4):339–42. 10.1016/s0735-6757(03)00037-8 . Cite Share Download PDF Status: Published Journal Publication published 13 May, 2025 Read the published version in Italian Journal of Pediatrics → Version 1 posted Editorial decision: Major revision 27 Aug, 2024 Reviewers agreed at journal 06 Aug, 2024 Reviewers invited by journal 06 Aug, 2024 Editor assigned by journal 01 Aug, 2024 First submitted to journal 30 Jul, 2024 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-4753251","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":336625352,"identity":"3209174d-c86a-47e6-96d7-c1057513c90f","order_by":0,"name":"Chien-Heng Lin","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chien-Heng","middleName":"","lastName":"Lin","suffix":""},{"id":336625353,"identity":"65cc5c03-f574-4e71-89ce-ef4bdbe674e0","order_by":1,"name":"Ru-Huei Fu","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ru-Huei","middleName":"","lastName":"Fu","suffix":""},{"id":336625354,"identity":"35cce17e-ba95-4248-889b-63631abb7b6f","order_by":2,"name":"I-Ching Chou","email":"","orcid":"","institution":"CMUH: China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"I-Ching","middleName":"","lastName":"Chou","suffix":""},{"id":336625355,"identity":"0389aea2-d6a9-44b5-affa-228ce7e44524","order_by":3,"name":"Yu-Tzu Chang","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu-Tzu","middleName":"","lastName":"Chang","suffix":""},{"id":336625356,"identity":"82f5ab0c-8121-4d11-b8bb-2dbc1e5b750c","order_by":4,"name":"Syuan-Yu Hong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYDCCA2DEzMDA3gPm8/ARr4XnDJjFw0aMFgawFokcCIegFr7jxx8eLvhlLScf+fbg4485djJsDMwPH93Ao0XyTELC4Zl96caGt/OSDQ5uSwY6jM3YOAePFoMDCQcO8/YcTtw4O8dM4uA2ZqAWHjZpvFrOP2yAaJl5BqSlnggtN5IZDvP8OJw4X4IHpOUwYS2SN54xHOZtSDc24MkxNji77TgPGzMBv/CdT3/8mecPMMTazxg+qNxWbc/P3vzwMT4tYMDYBgoHGI+ZkHIw+MPAIN9AlMpRMApGwSgYiQAA5GpOgO5/I64AAAAASUVORK5CYII=","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Syuan-Yu","middleName":"","lastName":"Hong","suffix":""}],"badges":[],"createdAt":"2024-07-17 03:30:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4753251/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4753251/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13052-025-01980-2","type":"published","date":"2025-05-13T15:57:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64386320,"identity":"cb4b24f2-b4a9-41ad-a8b3-ec0eba36ea44","added_by":"auto","created_at":"2024-09-12 12:35:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":187588,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study.\u003c/p\u003e","description":"","filename":"Figure1studyflowchart.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/73bc2103b936089f03e6b2a1.jpg"},{"id":64386318,"identity":"2aa3d17f-0cde-4e48-b5e8-ece53e4d71a2","added_by":"auto","created_at":"2024-09-12 12:35:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":63764,"visible":true,"origin":"","legend":"\u003cp\u003eHospitalization days and diagnosis time between M-AFP and NM-AFP\u003c/p\u003e","description":"","filename":"Fig2ADMdayandDxday.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/f7fb443015335295a1b18604.jpg"},{"id":64386319,"identity":"b5bbb9ea-27bc-40cf-bede-a10779c79d42","added_by":"auto","created_at":"2024-09-12 12:35:37","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":140819,"visible":true,"origin":"","legend":"\u003cp\u003eDetailed Interpretation and Figure Legends for MRI Images of selective patients with Myelitis. (A) Sagittal T2W (left) and STIR (right) MRI of the thoracolumbar spine in a 17-year-old female with multiple sclerosis. Vertebral levels T11, T12, and L1 are labeled, with red stars indicating hyperintense lesions due to demyelination. (B) Sagittal T2W (left) and STIR (right) MRI of the cervical spine of a 4-year-old male with Enterovirus D68 infection. Vertebral levels C4, C5, C6, and C7 are labeled, showing hyperintense signals indicative of myelitis. (C) Sagittal and axial T2-weighted MRI of the thoracolumbar spine of an 18-year-old female with Systemic Lupus Erythematosus. Vertebral levels T9, T10, T11, T12, and L1 are labeled. The sagittal view shows hyperintense lesions, and the axial view at T12-L1 highlights spinal cord inflammation consistent with myelitis. MRI, Magnetic Resonance Imaging; T2W, T2-Weighted; STIR, Short Tau Inversion Recovery; MS, Multiple Sclerosis; EV-D68, Enterovirus D68; SLE: Systemic Lupus Erythematosus\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/76970bbda25ecf3f930a2737.jpg"},{"id":64387961,"identity":"91aabf77-6692-47df-affa-2445fe9bf5cc","added_by":"auto","created_at":"2024-09-12 12:43:38","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":115522,"visible":true,"origin":"","legend":"\u003cp\u003eA 4-year-old girl with bone metastasis from right adrenal neuroblastoma. (A) Sagittal MRI showing a large, heterogeneous mass in the right adrenal gland, indicated by the red arrow\u003c/p\u003e\n\u003cp\u003e(B) Sagittal MRI showing multiple vertebral lesions with low itensities, marked by red asterisks (T7, T9 and T11). These lesions show altered signal intensity compared to normal vertebral marrow, indicating metastatic involvement.\u003c/p\u003e\n\u003cp\u003e(C) F-18 FDG Whole Body PET Scan: The areas of increased uptake correspond to sites of active tumor growth, including the primary adrenal mass, spine, and possibly other distant organs such as the liver or lymph nodes. The overall pattern of distribution suggests extensive dissemination of neuroblastoma cells\u003c/p\u003e\n\u003cp\u003e(D) Axial MRI at the T12 level showing a metastatic spread of neuroblastoma mass in the left epidural space (yellow arrow), leading to neurological symptoms such as pain, weakness and sensory deficits.\u003c/p\u003e\n\u003cp\u003eMRI, Magnetic Resonance Imaging; F-18 FDG, Fluorodeoxyglucose (F-18); PET, Positron Emission Tomography\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/a59dbe6948162aaca982bd17.jpg"},{"id":64386321,"identity":"5baf26c7-9a1d-4436-b5d8-36a2e158210f","added_by":"auto","created_at":"2024-09-12 12:35:38","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":124078,"visible":true,"origin":"","legend":"\u003cp\u003eMRI and Electrophoresis Findings in Patients with Traumatic Injury (A) and Guillain-Barre Syndrome (B-D):\u003c/p\u003e\n\u003cp\u003e(A) The Sagittal T2-weighted MRI of a 3-year-old boy who suffered from a traffic injury. The red arrow indicates a visible injury at the C7-C8 vertebral level, suggesting a spinal cord injury secondary to the accident.\u003c/p\u003e\n\u003cp\u003e(B) The Sagittal T2-weighted MRI of a 17-year-old girl with GBS. Yellow arrows highlight spinal nerve root enhancement at the T10 and T11 vertebral levels, indicating inflammation and demyelination associated with GBS.\u003c/p\u003e\n\u003cp\u003e(C) Yellow arrows in the Axial T2-weighted MRI indicate nerve root enhancements, consistent with the inflammatory process of GBS\u003c/p\u003e\n\u003cp\u003e(D) The gel of Serum protein electrophoresis shows an abnormal gamma (γ) band, indicative of an immune response, the autoimmune nature of GBS\u003c/p\u003e\n\u003cp\u003eMRI, Magnetic Resonance Imaging; GBS, Guillain-Barre Syndrome; T2W, T2-Weighted\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/78b0af6eabc42d366a3ab23d.jpg"},{"id":83068093,"identity":"5c2c3c85-4761-4994-a746-473eee157cf6","added_by":"auto","created_at":"2025-05-19 16:10:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1122691,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4753251/v1/f401df76-b871-4da4-9795-c578e202ad4a.pdf"}],"financialInterests":"","formattedTitle":"Analysis of the Causes and Phenotypic Variations of Acute flaccid paralysis with and without myelitis in a Pediatric Hospital Setting in Taiwan","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAcute flaccid paralysis (AFP) is a clinical syndrome characterized by the rapid onset of weakness or paralysis with reduced muscle tone in the absence of other obvious causes, such as trauma [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It represents a critical medical emergency due to its potential to progress rapidly and cause significant morbidity and mortality. The spectrum of conditions presenting with AFP is broad, encompassing various infectious, inflammatory, autoimmune, and metabolic etiologies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Among these, myelitis, an inflammatory condition affecting the spinal cord, is a significant cause of AFP. Myelitis can result from a variety of underlying causes, including viral infections, autoimmune diseases, and demyelinating disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, AFP can also occur without myelitis, where the underlying etiologies are diverse and can include neuromuscular junction disorders, peripheral neuropathies, metabolic disturbances, and even hematologic malignancies. Conditions such as Guillain-Barre syndrome (GBS), polymyositis (PM), and hypokalemic periodic paralysis (hypoPP) are notable examples that must be considered in the differential diagnosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The diagnostic challenge is to accurately identify the underlying cause of AFP to initiate appropriate treatment promptly.\u003c/p\u003e \u003cp\u003eUnderstanding the demographic and clinical characteristics of patients with AFP, along with detailed analysis of laboratory findings and identified causes, can significantly enhance diagnostic accuracy and patient outcomes. Previous studies have primarily focused on either AFP with myelitis or specific conditions within the NM-AFP, but comprehensive comparisons between these two categories remain limited. This study aims to fill this gap by providing a comparative analysis of AFP with and without myelitis, focusing on demographic data, clinical presentations, laboratory findings, and underlying causes. By delineating the distinct profiles of these two groups, we seek to improve the diagnostic approach and clinical management of AFP. The ultimate goal is to ensure that patients receive timely and appropriate interventions, reducing the risk of long-term complications and enhancing overall prognosis.\u003c/p\u003e"},{"header":"2. Material and Methods","content":"\u003cp\u003eThis study analyzed the demographic and clinical characteristics of patients with AFP with and without myelitis. Data were collected from medical records of patients diagnosed between 2012 and 2021. The study included a total of 39 patients, divided into two groups: those with myelitis (M-AFP, n=22) and those without myelitis (NM-AFP, n=17).\u003c/p\u003e\n\u003cp\u003e2.1 Study Population:\u003c/p\u003e\n\u003cp\u003eParticipants were categorized based on the presence or absence of myelitis. Patients with myelitis were identified through clinical symptoms and confirmed by MRI findings, while those without myelitis were diagnosed based on clinical presentation and other diagnostic tools.\u003c/p\u003e\n\u003cp\u003e2.2 Ethical Approval and Data Collection:\u003c/p\u003e\n\u003cp\u003eThis study received approval from the Institutional Review Board of China Medical University Children\u0026rsquo;s Hospital (# DMR-113-041/CMUH113-REC2-029). In this retrospective cohort study, we aimed to explore the demographic and clinical characteristics of patients with acute flaccid paralysis, as well as their underlying causes and their approaches to diagnosis. We have adopted a medical record screening strategy and used a big data system to target the pediatric patients who came to our hospital for medical treatment in the past 10 years (Between January 1, 2012 and December 31, 2021). The keywords in their chief medical complaints are: (1) Limb or muscle weakness (2) Limb or muscle hemiplegia (3) Immobility (4) Limb pain (5) Feeling of \"paralysis\" or \"numbness\". Conduct in-depth comparison based on the keywords (1)-(5) to obtain 14,500 pieces of information, and further screen patients who meet the conditions of this study (Figure 1). Additionally, demographic data, including sex and age of onset, were recorded. Clinical characteristics, such as symptoms at onset, season of onset, and history of illness within two months prior to onset, were documented. Laboratory results, including cerebrospinal fluid (CSF), white blood cell count (WBC) and protein levels, were also collected.\u003c/p\u003e\n\u003cp\u003e2.3 Exclusion Criteria: Exclusions were made for patients who either:\u003c/p\u003e\n\u003cp\u003e2.3.1 Children who meet the definition of Benign acute childhood myositis (BACM) [7]. BACM is a self-limiting inflammatory muscle condition that primarily affects children. The condition tends to present itself during or shortly after a viral illness. Key features of BACM include:\u003c/p\u003e\n\u003cp\u003e2.3.1.1 Muscle Pain: Typically severe and localized to the calves, causing difficulty in walking.\u003c/p\u003e\n\u003cp\u003e2.3.1.2 Age Group: Most commonly affects school-aged children.\u003c/p\u003e\n\u003cp\u003e2.3.1.3 Viral Association: Often follows an upper respiratory tract infection or influenza.\u003c/p\u003e\n\u003cp\u003e2.3.1.4 Duration: Symptoms generally resolve within a few days to a week without specific treatment.\u003c/p\u003e\n\u003cp\u003e2.3.1.5 Laboratory Findings: Elevated serum creatine kinase levels are often observed, indicating muscle damage.\u003c/p\u003e\n\u003cp\u003e2.3.1.6 Clinical Course: BACM is considered benign and does not lead to long-term muscle complications.\u003c/p\u003e\n\u003cp\u003e2.3.2\u0026nbsp;Muscle or limb pain due to trauma of any cause (e.g., fractures, sprains, and contusions)\u003c/p\u003e\n\u003cp\u003e2.3.3 Temporary limb weakness caused by acute metabolic or neurological events (e.g., Todd's paralysis, hypoglycemia).\u003c/p\u003e\n\u003cp\u003e2.3.4 Cachexia caused by major diseases (e.g., malignant tumors, immune deficiency).\u003c/p\u003e\n\u003cp\u003e2.3.5 \"Reluctance to move\" caused by psychological or mental factors (e.g., somatosensory mental illness or chronic fatigue syndrome, depression, and conversion disorder).\u003c/p\u003e\n\u003cp\u003e2.3.6 Others whose diagnosis cannot be established.\u003c/p\u003e\n\u003cp\u003e2.4 Statistical Analysis:\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were used to summarize the demographic and clinical characteristics of the two groups. Continuous variables were reported as mean \u0026plusmn; standard deviation, and categorical variables were presented as frequencies and percentages. The chi-square test or Fisher's exact test was used to compare categorical variables, while the independent t-test was used for continuous variables. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e2.5\u0026nbsp;Identification of Causes:\u003c/p\u003e\n\u003cp\u003eFor patients with myelitis, the underlying causes were identified using MRI (typically T2-weighted imaging combined with contrast-enhanced T1-weighted imaging and Short Tau Inversion Recovery, STIR) and other diagnostic tools. Similarly, the causes of AFP in patients without myelitis were determined using various diagnostic methods, including imaging studies, laboratory tests, and clinical criteria. In addition, differences in symptoms between individual patients were analyzed through medical records, and differences in causes, demographics, clinical manifestations, and diagnostic patterns of the two types of patients were investigated.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1 Demographic and Clinical Characteristics:\u003c/p\u003e\n\u003cp\u003eThe demographic and clinical characteristics of the study population are summarized in Table 1. The mean age of onset for M-AFP was 10.5 \u0026plusmn; 8.7 years, and for NM-AFP, it was 10.6 \u0026plusmn; 4.9 years (p = 0.96). There was no significant difference in sex distribution between the two groups (p = 0.85). The distribution of onset by season did not show a significant difference between M-AFP and NM-AFP (p \u0026gt; 0.05 for all comparisons).All patients with myelitis presented with limb weakness (100%), compared to 16 patients (94%) in NM-AFP (p = 0.99). Limb numbness was significantly more common in M-AFP (91% vs. 29%, p \u0026lt; 0.001), whereas myalgia was more prevalent in NM-AFP (88% vs. 23%, p \u0026lt; 0.001). The mean CSF WBC count was higher in M-AFP (52.4 \u0026plusmn; 62.7 cells/\u0026mu;L) compared to NM-AFP (27.6 \u0026plusmn; 50.2 cells/\u0026mu;L), but this difference was not statistically significant (p = 0.22). The mean CSF protein levels were similar between the two groups (61.8 \u0026plusmn; 40.9 mg/dL vs. 68.1 \u0026plusmn; 47.6 mg/dL, p = 0.65).\u003c/p\u003e\n\u003cp\u003e3.2 Underlying Causes:\u003c/p\u003e\n\u003cp\u003eTables 2 and 3 present the identified causes of acute myelitis and AFP without myelitis, respectively. In M-AFP, the causes included multiple sclerosis, herpes simplex virus, Behcet's disease, enterovirus, systemic lupus erythematosus, influenza A, spinal subdural hematoma, and Enterovirus D68. In NM-AFP, the causes included polymyositis, porphyria, juvenile dermatomyositis, myasthenia gravis, neuroblastoma, acute lymphoblastic leukemia (ALL), GBS, spinal cord injury, and hypoPP\u003c/p\u003e\n\u003cp\u003e3.3 Hospitalization Days and Diagnosis Time:\u003cbr /\u003e\u003cstrong\u003eFigure 2\u003c/strong\u003e presents box plots comparing the number of hospitalization days and diagnosis time between the two groups:\u003c/p\u003e\n\u003cp\u003e3.3.1 Hospitalization Days: In NM-AFP, the median number of hospitalization days was approximately 8 days, with an interquartile range (IQR) of about 3 to 15 days, including outliers extending up to 105 days. In contrast, M-AFP had a median of roughly 11 days, an IQR of about 7 to 15 days, and outliers reaching up to 85 days. The p-value of 0.714 indicates no statistically significant difference between the two groups regarding hospitalization days.\u003c/p\u003e\n\u003cp\u003e3.3.2 Diagnosis Time: NM-AFP had a median diagnosis time of around 22 days, with an IQR spanning from about 7 to 65 days, and outliers extending up to 150 days. M-AFP showed a much faster median diagnosis time of approximately 7 days, an IQR of about 2 to 12 days, and outliers reaching up to 130 days. The p-value of 0.818 suggests no statistically significant difference between the groups concerning diagnosis time.\u003c/p\u003e\n\u003cp\u003e3.4 Statistical Significance of Underlying Causes:\u003c/p\u003e\n\u003cp\u003eThe prevalence of other identified causes of infection was significantly higher in M-AFP (36% vs. 0%, p = 0.005). Similarly, the identification of underlying causes for diseases was significantly higher in NM-AFP (94% vs. 59%, p = 0.013).\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study provides a comprehensive analysis of the demographic and clinical characteristics, symptoms, laboratory results, and underlying causes of M-AFP and NM-AFP. The findings underscore significant clinical differences between these two groups, offering valuable insights for clinical practice and further research.\u003c/p\u003e\n\u003cp\u003e4.1 Demographic and Clinical Characteristics:\u003c/p\u003e\n\u003cp\u003eThe demographic data revealed no significant difference in the mean age of onset or sex distribution between patients with and without myelitis. Despite no previous research directly comparing demographic data of M-AFP and NM-AFP, studies focused on Guillain-Barr\u0026eacute; syndrome [8] and AFP of unknown etiology [9] indicate that AFP can affect individuals of any age and gender, highlighting its non-discriminatory nature. Understanding these demographic characteristics is crucial as it broadens the differential diagnosis in clinical settings, ensuring that clinicians consider a wide range of potential underlying conditions when diagnosing AFP. A notable finding is the significant difference in initial symptoms between M-AFP and NM-AFP. Patients with myelitis frequently presented with limb weakness and numbness, symptoms commonly associated with the inflammation and damage to the spinal cord characteristic of myelitis [10-12]. This is contrasted by NM-AFP, which reported higher instances of myalgia, characteristic of idiopathic inflammatory myopathies such as polymyositis and juvenile dermatomyositis [13,14]. This differentiation in symptoms guides clinicians towards the appropriate diagnostic pathway and helps prioritize investigations that can confirm the underlying cause.\u003c/p\u003e\n\u003cp\u003e4.2 Laboratory Results:\u003c/p\u003e\n\u003cp\u003eAnalysis of CSF showed higher mean WBC counts in M-AFP compared to NM-AFP, although the difference was not statistically significant. Elevated CSF WBC counts in myelitis patients can indicate an inflammatory or infectious process within the CNS [15]. While the study did not find significant differences in CSF protein levels between M-AFP and NM-AFP, elevated protein levels remain a critical marker in diagnosing CNS pathologies [16,17].\u003c/p\u003e\n\u003cp\u003e4.3 Underlying Causes:\u003c/p\u003e\n\u003cp\u003eThe etiology of AFP in our cohort was diverse. In M-AFP, conditions such as multiple sclerosis, herpes simplex virus, Behcet\u0026rsquo;s disease, systemic lupus erythematosus, influenza A, spinal subdural hematoma, enterovirus-D68, and enterovirus A71 were identified \u003cstrong\u003e(Figure 3)\u003c/strong\u003e [16,18-20]. This wide spectrum of infectious, inflammatory, and autoimmune conditions leading to myelitis underscores the need for comprehensive diagnostic approaches, including MRI and specific laboratory tests (e.g., CSF analysis, viral PCR tests, autoimmune markers, and other blood tests) to accurately identify the underlying cause. Conversely, NM-AFP presented a broader array of underlying causes, highlighting the heterogeneity of this patient group. Conditions such as PM, porphyria, JDM, myasthenia gravis, neuroblastoma, ALL, GBS, spinal cord injury, and hypoPP were identified [21-24]. The variety of these conditions indicates that clinicians must maintain a high index of suspicion for a wide range of potential etiologies, including hematology and oncology diseases like ALL and neuroblastoma [25,26]. This is crucial because hematologic disorders can present with neurological manifestations that may initially be misinterpreted as primary neurological conditions.\u003c/p\u003e\n\u003cp\u003e4.4 Clinical Significance of Hematologic Disorders: Examples of ALL and Neuroblastoma:\u003c/p\u003e\n\u003cp\u003eHematologic disorders, such as neuroblastoma and ALL, are particularly noteworthy due to their potential to cause significant morbidity and mortality if not promptly diagnosed and treated. ALL can present with various neurological manifestations, such as headaches, seizures, and focal neurological deficits, due to leukemic infiltration, treatment-related neurotoxicity, or secondary infections. These symptoms can mimic other neurological conditions and lead to an initial misdiagnosis as a primary neurological disorder rather than a hematologic malignancy [27]. Nonetheless, the presentation of AFP in ALL can often be subtle, requiring a high index of suspicion. Neuroblastoma is a malignant tumor arising from neural crest cells, typically affecting young children. It can lead to AFP through various mechanisms, including direct compression of the spinal cord or nerve roots, paraneoplastic syndromes (e.g., opsoclonus-myoclonus syndrome), and infiltration of the spinal canal \u003cstrong\u003e(Figure 4)\u003c/strong\u003e [28]. This tumor's diverse presentations often include acute weakness or paralysis, sometimes leading to initial misdiagnosis as a primary neurological disorder [29]. By using neuroblastoma and ALL as examples, we underscore the importance of considering hematologic disorders in the differential diagnosis of AFP. This approach ensures that clinicians can identify and manage these potentially life-threatening conditions effectively, improving patient outcomes.\u003c/p\u003e\n\u003cp\u003e4.5 Diagnostic Tools for NM-AFP:\u003c/p\u003e\n\u003cp\u003eGiven the diverse underlying causes in NM-AFP, a broad range of diagnostic tools must be considered. For instance, neuroimaging, such as MRI, is essential for detecting structural abnormalities, including tumors and spinal cord injuries \u003cstrong\u003e(Figure 5A)\u003c/strong\u003e. Muscle biopsy and serological tests for muscle-specific antibodies are crucial for diagnosing conditions like PM and JDM [30,31]. Electromyography, nerve conduction studies, spinal MRI and CSF-Immunofixation electrophoresis are vital for diagnosing peripheral neuropathies such as GBS (\u003cstrong\u003eFigure 5B-D\u003c/strong\u003e) and porphyria [32,33]. In cases of suspected hematologic disorders, initial laboratory tests such as a complete blood count and peripheral blood smear can provide crucial clues. Further confirmation through bone marrow biopsy and flow cytometry is often required to diagnose conditions like ALL [34]. For hypoPP, a detailed history and blood tests during an episode of paralysis are essential to confirm the diagnosis [35].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.6 Limitations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. The relatively small sample size may limit the generalizability of the findings. Additionally, the retrospective nature of the study and reliance on medical records may introduce selection bias and inaccuracies in data recording. Furthermore, because software was used to assist in screening a large number of case data over the past 10 years using keywords instead of manual screening, the number of subjects included and excluded in the experiment is very likely to be different from the actual number of patients. Future prospective studies with larger sample sizes are needed to validate these findings and further explore the differences between AFP with and without myelitis.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eThis study provides a detailed comparative analysis of AFP with and without myelitis, highlighting significant differences in clinical presentation, laboratory findings, and underlying causes. Patients with myelitis (M-AFP) frequently presented with limb numbness and had higher cerebrospinal fluid white blood cell counts, though the latter was not statistically significant. In contrast, patients without myelitis (NM-AFP) commonly experienced myalgia and had a broader array of underlying conditions, including polymyositis, Guillain-Barre syndrome, and various hematologic disorders. These findings emphasize the importance of a tailored diagnostic approach to enhance the accuracy of diagnosis and the timeliness of interventions. While the study\u0026apos;s retrospective nature and small sample size are limitations, the insights gained underscore the need for comprehensive diagnostic strategies to manage AFP effectively. Future research should focus on larger, prospective studies to validate these findings and further refine clinical management protocols, ultimately aiming to improve patient outcomes and reduce the risk of long-term complications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003col\u003e\n \u003cli\u003eAChR-Ab: Acetylcholine Receptor Antibodies\u003c/li\u003e\n \u003cli\u003eAFP: Acute Flaccid Paralysis\u003c/li\u003e\n \u003cli\u003eALL: Acute Lymphoblastic Leukemia\u003c/li\u003e\n \u003cli\u003eBACM: Benign Acute Childhood Myositis\u003c/li\u003e\n \u003cli\u003eCNS: Central Nervous System\u003c/li\u003e\n \u003cli\u003eCSF: Cerebrospinal Fluid\u003c/li\u003e\n \u003cli\u003eCT: Computed Tomography\u003c/li\u003e\n \u003cli\u003eDTR: Deep Tendon Reflexes\u003c/li\u003e\n \u003cli\u003eEV: Enterovirus\u003c/li\u003e\n \u003cli\u003eEV-D68: Enterovirus D68\u003c/li\u003e\n \u003cli\u003eF-18 FDG: Fluorodeoxyglucose (F-18)\u003c/li\u003e\n \u003cli\u003eGBS: Guillain-Barre Syndrome\u003c/li\u003e\n \u003cli\u003ehypoPP: Hypokalemic Periodic Paralysis\u003c/li\u003e\n \u003cli\u003eIQR: Interquartile Range\u003c/li\u003e\n \u003cli\u003eJDM: Juvenile Dermatomyositis\u003c/li\u003e\n \u003cli\u003eMG: Myasthenia Gravis\u003c/li\u003e\n \u003cli\u003eMRI: Magnetic Resonance Imaging\u003c/li\u003e\n \u003cli\u003eMS: Multiple Sclerosis\u003c/li\u003e\n \u003cli\u003eNM-AFP: Acute Flaccid Paralysis without Myelitis\u003c/li\u003e\n \u003cli\u003ePCR: Polymerase Chain Reaction\u003c/li\u003e\n \u003cli\u003ePET: Positron Emission Tomography\u003c/li\u003e\n \u003cli\u003ePM: Polymyositis\u003c/li\u003e\n \u003cli\u003eSLE: Systemic Lupus Erythematosus\u003c/li\u003e\n \u003cli\u003eSTIR: Short Tau Inversion Recovery\u003c/li\u003e\n \u003cli\u003eT2W: T2-Weighted\u003c/li\u003e\n \u003cli\u003eWBC: White Blood Cell\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn behalf of all the authors (the names are as follows: SYH, RHF, YTC, ICC and CHL), we extend our utmost gratitude to the medical and financial support of China Medical University Hospital and China Medical University Children\u0026rsquo;s Hospital (DMR-113-041/CMUH113-REC2-029) to the completion of this article. We express our sincere appreciation to the Department of Imaging Medicine at China Medical University Hospital. Their invaluable insights and timely guidance have been instrumental in resolving intricate diagnostic cases and facilitating the interpretation of medical images. It is unequivocally due to their invaluable assistance that this article has reached its successful culmination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSYH provided treatment to the patient, collected the data and wrote the draft. RHF and YTC participated in the design of the study and wrote the manuscript. ICC and CHL provided their experience for the patient\u0026rsquo; s collection and modified the manuscript accordingly. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for discussion of the clinical history was provided by the medical records. The study protocol was approved by the Ethics Review Board of the China Medical University ethics committee (Approval #\u0026nbsp;DMR-113-041/CMUH113-REC2-029). Written informed consent of participation was obtained from the legal guardians. A statement to confirm that all methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient\u0026rsquo;s guardians have consented to submission of this study to the journal, and we have obtained a written informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHosoya M. 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Am J Emerg Med. 2003;21(4):339\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0735-6757(03)00037-8\u003c/span\u003e\u003cspan address=\"10.1016/s0735-6757(03)00037-8\" 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":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acute flaccid paralysis, myelitis, children","lastPublishedDoi":"10.21203/rs.3.rs-4753251/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4753251/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Acute flaccid paralysis (AFP) is a clinical syndrome marked by the sudden onset of muscle weakness or paralysis, posing a critical medical emergency due to its potential for rapid progression and significant morbidity and mortality. This study investigates the demographic and clinical characteristics, laboratory findings, and underlying causes of AFP in patients with and without myelitis (M-AFP and NM-AFP, respectively).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eData were retrospectively collected from 39 patients diagnosed between 2012 and 2021, divided into M-AFP (n=22) and NM-AFP (n=17) groups. Patients with myelitis were identified via clinical symptoms and magnetic resonance imaging findings, while those without myelitis were diagnosed through clinical presentation and various diagnostic tools. Key demographic data, clinical characteristics, and laboratory results, such as cerebrospinal fluid white blood cell count and protein levels, were analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe study identified distinct etiologies for M-AFP, including multiple sclerosis, herpes simplex virus, and enterovirus, among others. In contrast, NM-AFP was associated with conditions such as polymyositis, Guillain-Barre syndrome, and hypokalemic periodic paralysis. Statistical analysis revealed significant differences in symptoms at onset, with limb numbness more prevalent in M-AFP and myalgia more common in NM-AFP. Although cerebrospinal fluid white blood cell counts were higher in M-AFP, the difference was not statistically significant.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e This comprehensive analysis highlights the diverse etiologies and clinical presentations of AFP, emphasizing the need for tailored diagnostic strategies to enhance patient care and outcomes.\u003c/p\u003e","manuscriptTitle":"Analysis of the Causes and Phenotypic Variations of Acute flaccid paralysis with and without myelitis in a Pediatric Hospital Setting in Taiwan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-12 12:35:33","doi":"10.21203/rs.3.rs-4753251/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2024-08-27T08:44:05+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-08-06T11:14:04+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-06T10:05:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-01T09:31:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2024-07-30T04:13:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"46525c55-7ca8-492c-8e15-85a45b8ab50f","owner":[],"postedDate":"September 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-19T16:07:07+00:00","versionOfRecord":{"articleIdentity":"rs-4753251","link":"https://doi.org/10.1186/s13052-025-01980-2","journal":{"identity":"italian-journal-of-pediatrics","isVorOnly":false,"title":"Italian Journal of Pediatrics"},"publishedOn":"2025-05-13 15:57:54","publishedOnDateReadable":"May 13th, 2025"},"versionCreatedAt":"2024-09-12 12:35:33","video":"","vorDoi":"10.1186/s13052-025-01980-2","vorDoiUrl":"https://doi.org/10.1186/s13052-025-01980-2","workflowStages":[]},"version":"v1","identity":"rs-4753251","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4753251","identity":"rs-4753251","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}