Sentinel Symptom Burden and Clinical Severity at Presentation in Pediatric Intracranial Aneurysms: A Retrospective Cohort Study from a Low- and Middle-Income Country

Sentinel Symptom Burden and Clinical Severity at Presentation in Pediatric Intracranial Aneurysms: A Retrospective Cohort Study from a Low- and Middle-Income Country | 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 Sentinel Symptom Burden and Clinical Severity at Presentation in Pediatric Intracranial Aneurysms: A Retrospective Cohort Study from a Low- and Middle-Income Country Oumou Kalsoum Mbacke, Akaash Suresh, Harshit Polavarapu, Omar Thiam, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9140361/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract INTRODUCTION In low- and middle-income countries (LMICs), early bedside assessment is critical for informing triage decisions when imaging and subspecialty care are limited. The present study evaluated whether the burden of presenting sentinel symptoms is associated with clinical severity at presentation among pediatric patients with intracranial aneurysms. METHODS A retrospective analysis was performed on 22 pediatric patients (≤ 18 years) with radiologically confirmed intracranial aneurysms treated at a tertiary LMIC center between 2013 and 2024. Five presenting sentinel symptoms such as headache, vomiting, seizures, visual disturbances, and altered consciousness, were collected from clinical records, and symptom burden was defined as the total symptom count (0–5). The primary outcomes were WFNS grade and Fisher grade at presentation. Ordinal logistic regression was used to model the association between symptom count and WFNS grade, adjusting for log-transformed admission delay. RESULTS The mean age of the cohort was 13.3 ± 4.9 years. Presenting symptoms included headache in all patients (100%), vomiting in 12 (55%), seizures in 7 (32%), altered consciousness in 6 (27%), and visual disturbances in 2 (9%). Patients presented with 1 to 5 sentinel symptoms (mean 2.4 ± 1.2). WFNS grades at presentation were distributed as follows: Grade 1 in 5 patients (23%), Grade 2 in 1 patient (5%), Grade 3 in 10 patients (45%), and Grade 4 in 6 patients (27%). Ordinal logistic regression demonstrated that each additional presenting symptom was associated with a higher WFNS grade (OR 3.71, 95% CI 1.26–10.89; p = 0.017), with McFadden’s pseudo-R² approximately 0.20. Fisher grade was not associated with WFNS grade (p = 0.140). Admission delay averaged 14.0 ± 27.1 days (range 1–120), and log-transformed admission delay was not associated with WFNS grade (OR 1.12, 95% CI 0.56–2.26; p = 0.750). CONCLUSION In this cohort, a higher burden of presenting sentinel symptoms was associated with increased WFNS grade at presentation. These findings support further evaluation of symptom count as a clinical marker of initial neurological severity in pediatric intracranial aneurysms, particularly within resource-limited settings. Pediatric intracranial aneurysm Sentinel symptoms WFNS grade Fisher grade Clinical severity Triage Low- and middle-income countries Global neurosurgery Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Pediatric intracranial aneurysms (PIAs) are uncommon, accounting for less than 5% of all intracranial aneurysms. The majority of affected children present with ruptured aneurysms and subarachnoid hemorrhage, resulting in significant morbidity.¹ – ³ These challenges are exacerbated in Low- and Middle-Income Countries (LMICs), where a shortage of neurosurgeons and limited access to diagnostic imaging contribute to delays in diagnosis and intervention. 4–7 In these situations, frontline providers are often required to make early clinical decisions devoid of immediate access to imaging or specialist consultation, relying solely on clinical assessment to identify high-risk children. The World Federation of Neurosurgical Societies (WFNS) grading scale assesses the initial severity of aneurysmal subarachnoid hemorrhage and helps guide urgent care decisions. 8,9 In LMICs, this scale often cannot be used right away, as grading typically waits until after transfer to specialized centers. 4,5 This delay discloses a critical gap: the need for simple, cost-free bedside indicators to help identify children at high risk during early warning symptoms. These symptoms such as sudden severe headache, vomiting, or seizures, may warn of up to 40% of aneurysmal ruptures and can signal minor leaks from unstable aneurysms. 10 While the significance of isolated warning symptoms in adults is debated, the effect of multiple warning signs has not been fully studied. 11,12 Multiple pre-rupture symptoms may mean repeated instability or worsening neurologic involvement. This is especially important in pediatric cases, where symptoms are often unusual, making early recognition harder for general providers. In LMIC emergency settings, a simple count of sentinel symptoms may serve as a practical indicator of aneurysmal instability and severity. This study evaluates whether the number of sentinel symptoms is associated with initial WFNS grade in a pediatric intracranial aneurysm cohort from an LMIC. METHODS Study Design and Setting This study was a retrospective observational cohort analysis of pediatric patients with intracranial aneurysms evaluated at a single tertiary referral neurosurgical center in a low- and middle-income country. Patients presenting between January 1, 2013, and December 31, 2024, were eligible for inclusion. Institutional ethics committee approval was obtained, and informed consent was waived due to the retrospective design and use of deidentified data. Potential cases were identified through a systematic review of institutional neurosurgical logs, inpatient registries, and radiological imaging archives. Patients were managed according to local institutional protocols for suspected intracranial aneurysm and subarachnoid hemorrhage. Clinical variables and timing data were derived from contemporaneous documentation in the electronic medical record. Patient Identification and Cohort Derivation During the study period, all pediatric patients with radiologically suspected intracranial aneurysms were screened. Radiological confirmation was established using computed tomography angiography or digital subtraction angiography. Patients were included if they were 18 years of age or younger at presentation and had documented WFNS grade, complete sentinel symptom documentation, and recorded timing from symptom onset to hospital presentation. Patients were excluded if documentation was insufficient to derive the primary outcome or if prespecified predictors were missing for regression modeling. All eligible consecutive cases during the study period were included without sampling. Regression analyses were performed using complete-case methodology, and the number of observations contributing to each model is reported in the Results. No imputation was performed. Variables and Definitions The primary outcome was neurological severity at presentation, measured using the World Federation of Neurosurgical Societies (WFNS) grading scale. WFNS grade was abstracted from contemporaneous clinician documentation at the time of initial evaluation and was not retrospectively reassigned. For analysis, WFNS grade was modeled both as an ordinal outcome reflecting ordered severity categories (WFNS grades 1–4) and as a binary outcome categorized as good-grade (WFNS 1–2) versus poor-grade (WFNS 3–4) to enhance clinical interpretability and assess robustness of associations. The secondary outcome was radiological severity of subarachnoid hemorrhage measured using the Fisher grading scale on initial computed tomography imaging. Five sentinel presenting symptoms were abstracted from emergency department and neurosurgical documentation at presentation: headache, vomiting, seizures, visual disturbances, and altered consciousness. Each symptom was coded as present or absent based on physician and nursing documentation. A composite symptom burden score was defined a priori as the total number of sentinel symptoms present at presentation, yielding a range from 0 to 5. Headache was present in all patients and therefore, did not differentiate severity; however, it was retained in descriptive summaries for completeness. Admission delay was defined as the time in days from symptom onset to hospital presentation. Because admission delay demonstrated a right-skewed distribution, it was log-transformed using the natural logarithm for regression modeling. Untransformed delay was summarized descriptively to preserve clinical interpretability. Age at presentation was recorded in years and summarized descriptively. Given the cohort size and the rarity of pediatric intracranial aneurysms, regression modeling was limited to the prespecified predictors of symptom burden and log-transformed admission delay to minimize overfitting. Data Collection and Bias Considerations Data were obtained from retrospective review of emergency department records, neurology and neurosurgery consultations, inpatient documentation, and imaging reports. Sentinel symptoms were abstracted from structured fields and narrative notes; when onset timing was unclear, the earliest documented onset was used. Symptom definitions were standardized before abstraction to minimize misclassification. Confounding was addressed by jointly modeling symptom burden and log-transformed admission delay in prespecified regression analyses. Statistical Analysis Continuous variables were summarized using medians with ranges or interquartile ranges as appropriate for non-normal distributions. Categorical variables were reported as frequencies and percentages. Descriptive visualizations were generated to illustrate age distribution, symptom clustering across WFNS grades, and patterns of admission delay. To evaluate predictors of neurological severity at presentation, an ordinal logistic regression model using the proportional odds framework was fitted with WFNS grade as the ordered dependent variable and symptom burden and log-transformed admission delay as predictors. A secondary binary logistic regression model was fitted using the same predictors, with WFNS grade categorized as good or poor. A separate ordinal logistic regression model was fitted with Fisher grade as the outcome to evaluate associations between symptom burden and radiological hemorrhage severity. Effect estimates are reported as odds ratios with 95% confidence intervals. Model fit was summarized using McFadden’s pseudo-R². The proportional odds assumption was evaluated using the Brant test. If the proportional odds assumption was violated, results were interpreted cautiously and compared with the binary logistic regression model. All tests were two-sided, and statistical significance was defined as p < 0.05, with interpretation guided primarily by effect estimates and confidence intervals. All analyses were performed using Python statistical libraries. RESULTS Clinical Severity at Presentation Twenty-two pediatric patients met the inclusion criteria during the study period. WFNS grades at presentation were distributed as follows: Grade 1 in 5 patients (22.7%), Grade 2 in 1 patient (4.5%), Grade 3 in 10 patients (45.5%), and Grade 4 in 6 patients (27.3%). No patient presented with WFNS Grade 5. When dichotomized into good-grade (WFNS 1–2) and poor-grade (WFNS 3–4), 6 patients (27.3%) were classified as good-grade and 16 patients (72.7%) as poor-grade. The mean age at presentation differed across severity groups. Patients with WFNS 1–2 had a mean age of approximately 16.8 years, whereas those with WFNS 3–4 had a mean age of approximately 12.5 years (Mann–Whitney U test, p ≈ 0.02). Sex distribution did not differ between groups; females comprised 50% of the WFNS 1–2 group and 56% of the WFNS 3–4 group (Fisher’s exact test, p > 0.99). Functional status at discharge, measured using the modified Rankin Scale (mRS), was 2.0 ± 2.0 among patients presenting with WFNS 1–2 and 3.4 ± 1.7 among those presenting with WFNS 3–4 (Mann–Whitney U test, p ≈ = 0.08). Age distribution by WFNS grade is shown in FIG. 1 . Figure 1 . Age distribution by WFNS grade Sentinel Symptom Burden and WFNS Grade All patients (22/22, 100%) reported headache at presentation. Additional presenting symptoms included vomiting in 12 patients (55%), seizures in 7 (32%), altered consciousness in 6 (27%), and visual disturbances in 2 (9%). The total number of sentinel symptoms per patient ranged from 1 to 5, with a mean of 2.4 ± 1.2 and a median of 2. Six patients (27%) presented with 1 symptom, 9 (41%) with 2 symptoms, 4 (18%) with 3 symptoms, 2 (9%) with 4 symptoms, and 1 patient (5%) with 5 concurrent symptoms. Among patients with WFNS 1–2 (n = 6), vomiting occurred in 3 patients (50.0%) and seizures in 2 (33.3%); none had visual disturbances or altered consciousness. Among patients with WFNS 3–4 (n = 16), vomiting occurred in 9 (56.3%), seizures in 5 (31.3%), visual disturbances in 2 (12.5%), and altered consciousness in 6 (37.5%). Mean symptom count was 1.8 ± 0.4 among patients with WFNS 1–2 and 2.4 ± 1.3 among those with WFNS 3–4. Comparison of symptom counts between groups using the Mann–Whitney U test yielded U ≈ 37.5 (p ≈ 0.44). Symptom prevalence by WFNS grade is shown in FIG.2. Admission Delay Mean admission delay from symptom onset to hospital presentation was 14.0 ± 27.1 days (range 1–120 days). The distribution was right-skewed, with a 25th percentile of 1 day, a median of 6.5 days, and a 75th percentile of 9.8 days. Admission delay did not differ significantly across individual WFNS grades (1–4). Comparison using the Kruskal–Wallis test yielded H ≈ 5.0 (p ≈ 0.17). When WFNS grades were dichotomized, patients with WFNS 1–2 (n = 6) had a mean admission delay of 13.0 ± 23.2 days (median 3.5 days), whereas those with WFNS 3–4 (n = 16) had a mean delay of 14.4 ± 29.1 days (median 8.5 days). Comparison using the Mann–Whitney U test yielded U ≈ 42.0 (p ≈ 0.68). Spearman correlation between WFNS grade (treated as ordinal) and admission delay was ρ ≈ −0.19 (p ≈ 0.40) on both the raw and log-transformed scales. Admission delay distributions are shown in FIG.3 , and the relationship between log-transformed admission delay and WFNS grade is shown in FIG.4 . Across the cohort, patients presented with a median of 2 sentinel symptoms (range 1–5). Six patients (27.3%) reported 1 symptom, 9 (40.9%) reported 2 symptoms, 4 (18.2%) reported 3 symptoms, 2 (9.1%) reported 4 symptoms, and 1 patient (4.5%) reported 5 concurrent symptoms. Headache was present in all patients (100%) in both the WFNS 1–2 and WFNS 3–4 groups. Among patients with WFNS 1–2, vomiting occurred in 3 of 6 (50.0%) and seizures in 2 of 6 (33.3%); no patient had visual disturbance or altered consciousness. Among patients with WFNS 3–4, vomiting occurred in 9 of 16 (56.3%), seizures in 5 of 16 (31.3%), visual disturbances in 2 of 16 (12.5%), and altered consciousness in 6 of 16 (37.5%). In ordinal logistic regression modeling WFNS grade as an ordered outcome, total presenting symptom count was associated with higher WFNS grade (OR 3.71, 95% CI 1.26–10.89; p = 0.017). Log-transformed admission delay was not associated with WFNS grade (OR 1.12, 95% CI 0.56–2.26; p = 0.75). McFadden’s pseudo-R² for the model was approximately 0.20. In binary logistic regression modeling WFNS 3–4 versus WFNS 1–2, each additional presenting symptom was associated with an OR of 2.17 (95% CI 0.66–7.15; p = 0.203). Log-transformed admission delay was not associated with binary WFNS status (OR 1.44, 95% CI 0.64–3.26; p = 0.376). McFadden’s pseudo-R² for the binary model was approximately 0.08. DISCUSSION Symptom Burden and Clinical Severity at Presentation In this pediatric cohort, where nearly half of the children presented in poor neurological grade (WFNS 3–4), the accumulation of sentinel symptoms emerged as a powerful marker of early clinical deterioration. The mean symptom count of 2.4 ± 1.2 indicates that most children arrived with more than one concerning feature, and our data demonstrate a clear gradient: children with three or more symptoms were disproportionately represented among the poor-grade presentations. The multivariable regression confirmed that each additional symptom increased the odds of a higher WFNS grade by nearly fourfold (OR 3.71; 95% CI 1.26–10.89; p = 0.017), a magnitude that carries practical bedside meaning as a single symptom increase nearly quadruples the risk of falling into a worse clinical grade. Children who accumulate ≥ 3 symptoms likely represent a clinically significant threshold warranting urgent triage, expedited imaging, or prioritized transfer. 8,13 That symptom count alone explained about 20% of the variance in WFNS grade, underscoring its value as an independent predictor in a population in which traditional markers behaved inconsistently. Equally important is what did not predict severity. Neither log-transformed admission delay nor Fisher grade significantly correlated with presented WFNS grade in our adjusted analyses, findings that distinguish this pediatric cohort from typical adult SAH patterns. 9 Although the median admission delay was substantial, reflecting well-known LMIC referral challenges, its lack of association with severity indicates that elapsed time from initial symptom to presentation is a poor surrogate for physiological decline in children. Prior pediatric literature has similarly shown that children often deteriorate rapidly and unpredictably, with symptom progression indicating shifts in intracranial dynamics rather than linear temporal decline, suggesting that poor-grade presentation is driven more by acute physiologic changes, such as building intracranial pressure and aneurysm instability, than by delays in presentation. 1,2,14,15 Thus, the cumulative symptom load in our cohort likely captures a physiologic progression from headache to vomiting to seizures, and ultimately to altered mental status, explaining both the nearly fourfold increase in odds of higher WFNS grade per additional symptom and its independence from referral delays. 12 Mechanistic Interpretation and Pediatric-Specific Pathophysiology The clustering of symptoms in our cohort—headache, vomiting, seizures, visual disturbances, and altered consciousness—maps onto distinct intracranial processes whose cumulative presence plausibly reflects advancing pathophysiology. Headache in pediatric aneurysms is generally attributable to meningeal irritation or acute distention of pain-sensitive vascular structures, while vomiting likely occurs as intracranial pressure increases and brainstem autonomic nuclei are compressed. 16,17 Seizures, which were not uncommon in this series, may have resulted from subcortical involvement and elevated intracranial pressure. 15 Visual complaints may indicate optic pathway compression from giant or fusiform aneurysms, morphologies that are disproportionately represented among pediatric populations compared with adults. 18 Finally, altered consciousness likely reflects global cerebral dysfunction due to impaired perfusion or acute hydrocephalus. 14 The presence of multiple concurrent symptoms in individual patients likely captures escalating physiological compromise and may serve as a practical, clinically relevant triage marker. Pediatric aneurysm biology likely amplifies these relationships. Children exhibit disproportionate rates of giant, fusiform, and dissecting aneurysms with mass-effect-driven presentations far more common than in adults. 19–21 These features predispose to symptom accumulation even before rupture, and once hemorrhage occurs, the combination of lower cranial compliance and more reactive inflammatory cascades can accelerate clinical deterioration. 15 Prior pediatric SAH work has emphasized that neurological grade correlates more closely with early physiological disruption than with hemorrhage volume, and our data mirror those observations. 2,3 Symptom burden, therefore, appears to integrate these layered physiological stressors into a readily observable clinical signal that may outperform more traditional structural markers in children. Symptom Count vs. Fisher Grade: Divergence and Implications One of the most striking findings of this study is the limited predictive value of Fisher grade for neurological severity at presentation. In our sample, Fisher grade was not significantly associated with WFNS grade, whereas the model including symptom count accounted for roughly 20% of the variance in presenting severity, representing a considerable improvement in explanatory value. This does not necessarily prove that imaging is intrinsically unreliable in pediatric aneurysms; instead, it may accentuate the likelihood that standard hemorrhage-based grading may fail to capture the full spectrum of pathophysiological variation in children. 2,22,23 Prior pediatric literature documented distinct patterns relative to adults, including a higher prevalence of partially thrombosed aneurysms and a substantial portion of non-ruptured or non-SAH presentations. 1,19 Because such structural and biological heterogeneity may modify how hemorrhage, mass effect, hydrocephalus, and cerebral edema evolve, it is plausible — though not yet empirically proven — that static CT-based hemorrhage distribution might underrepresent physiologic compromise in some cases. These unique morphological patterns weaken the reliance on hemorrhage-based grading alone. In LMIC contexts such as ours, this discrepancy is further magnified by delays in obtaining CT imaging, interruptions in referral pathways, and variability in initial imaging quality. 4,6,7 When radiologic assessment is delayed by hours to days, hemorrhage redistribution, evolving hydrocephalus, or clot degradation may diminish the reliability of the Fisher grade as an early triage tool. 9 Our findings that Fisher grade did not significantly predict WFNS grade, while simple symptom count did, suggest that clinical features may be more temporally stable and pathophysiologically sensitive indicators of severity in resource-limited settings. This divergence illustrates the potential value of integrating symptom-based approaches into early triage protocols, especially when radiologic severity is unavailable, delayed, or unreliable. Optimizing Early Neurosurgical Pathways Through Symptom-Guided Triage The observation that symptom count outperforms both imaging-based and time-based indicators of severity has direct operational implications for structuring early triage and referral processes across diverse neurosurgical systems. A standardized symptom-count field could be incorporated into existing triage forms at first-contact facilities, enabling clinicians to identify high-risk patients even when imaging is delayed or unavailable. 13,24 Similarly, pre-transfer checklists used by ambulance services and regional hospitals could include explicit symptom thresholds that trigger urgent communication with neurosurgical teams, while referral protocols could be designed to prompt consultation when two or more sentinel symptoms are present. 6,24 Evidence from neurosurgery systems research shows that streamlined clinical triggers and simplified referral algorithms can reduce diagnostic delays, improve transfer efficiency, and enhance early decision-making in settings where neurosurgical resources and imaging access vary widely. 13 Within this framework, identifying children with three or more symptoms at the initial point of care could justify bypassing intermediate facilities without neurosurgical capability and expedite transfer to centers capable of definitive management. Prior work in systems strengthening emphasizes that clinical early-warning tools can improve time-to-intervention and reduce preventable neurologic deterioration in both high- and low-resource environments, particularly for time-sensitive neurosurgical emergencies. 4,5 By providing a rapid, no-cost, clinically grounded indicator of physiological compromise, a symptom-based triage approach delivers a practical mechanism for improving referral accuracy, prioritizing limited critical-care capacity, and strengthening the early stages of pediatric aneurysm care pathway. LIMITATIONS This study must be interpreted within several limitations. First, as a retrospective chart review, all presenting symptoms were abstracted from clinical documentation, which introduces the possibility of underreporting, inconsistent terminology, and variable interpretation among providers, making documentation bias a central limitation of our analysis. Second, we were unable to collect angiographic characteristics such as aneurysm size, morphology, and location. These anatomical features are among the most robust predictors of severity and clinical grade in pediatric aneurysm cohorts, and the absence of these variables limits our ability to adjust for established confounders and to interpret whether symptom burden functions independently of these morphological factors. 3,20 Third, the small sample size of 22 children raises concern about potential model overfitting, particularly given the ratio of predictors to outcomes in the ordinal logistic regression. Although the model demonstrated acceptable stability, the findings should be validated in larger prospective or multicenter datasets. 8 Fourth, because the study was conducted at a single national referral hospital with distinct resource, referral, and documentation constraints, generalizability is limited. 4,6 Symptom-based triage performance may differ in settings with standardized neurological assessments, rapid imaging capacity, or broader availability of pediatric neurosurgical expertise, where faint deficits such as visual changes or early cognitive alterations may be detected more reliably. Finally, our symptom-count metric treats all symptoms equally, although symptoms such as seizures or altered consciousness likely carry greater prognostic importance than headache or vomiting; prospective studies should consider weighted scoring systems and standardized definitions to ensure reproducibility across centers. 15 These limitations indicate several directions for future work. Larger, prospective cohorts will be essential to validating whether symptom accumulation reliably predicts clinical severity and to determining how predictive effectiveness changes when anatomical variables, such as aneurysm size and morphology, are included. Prospective designs would also allow standardized documentation of sentinel symptoms at first contact, reducing the variability inherent in retrospective note review. Further studies should also evaluate how symptom-guided tools can be operationalized within actual referral networks, as early triage decisions strongly shape outcomes in pediatric neurovascular emergencies. 5,13 Implementation-science approaches, including health-systems modeling, could help determine how such tools might influence transfer timing, neurosurgical service load, ICU utilization, and cost-effectiveness across different health system structures. Together, these steps would advance the development of a practical, scalable early-severity marker that more accurately reflects the unique physiological and systems-level realities of pediatric aneurysm care. ​ CONCLUSION In this pediatric cohort, accumulation of sentinel symptoms was a meaningful marker of early neurological compromise, outperforming radiographic severity and admission delay in predicting WFNS grade at presentation. Each additional symptom was associated with nearly fourfold higher odds of worse clinical grade, and children with 3 or more symptoms represented a distinct high-risk subgroup, underscoring the dissociation between structural imaging markers and physiological severity in children. A standardized symptom-count metric may offer a pragmatic, accessible triage tool across referral settings, although prospective validation in larger populations is needed to clarify its role alongside established predictors. Declarations FUNDING The authors did not receive support from any organization for the submitted work. Author Contribution O.K.M. contributed to the introduction, discussion, and references and handled the statistics, preparation of figures. A.S and H.P contributed to the introduction, manuscript discussion, and references. O.T was involved in data collection and manuscript review. H.S.S and M.T provided manuscript reviews nd served as senior authors, directing and editing the manuscript throughout. All authors reviewed and approved the final version of the manuscript. Acknowledgement We thank Fann Teaching Hospital for their partnership and support. We are especially grateful to the individuals involved in data collection for this study. Their contributions were essential to the success of this research. References Sorteberg A, Dahlberg D. Intracranial nontraumatic aneurysms in children and adolescents. Curr Pediatr Rev. 2013;9(4):343–352. 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Child's Nerv Syst. 2024;40(8):2419–2429. doi:10.1007/s00381-024-06384-x Gupta S, Hauser BM, Catapano JS, et al. Rupture risk and outcomes of giant aneurysms in pediatric patients: a multi-institutional case series and systematic review. J Neurosurg Pediatr. 2023;33(3):276–284. doi:10.3171/2023.10.PEDS23296 Levy ML, Levy DM, Manna B. Pediatric cerebral aneurysm. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. de Aguiar GB, Ozanne A, Elawady A, et al. Intracranial aneurysm in the pediatric population: a single-center experience. Pediatr Neurosurg. 2022;57(4):270–278. doi:10.1159/000524523 Liang J, Bao Y, Zhang H, et al. Clinical features and treatment of pediatric intracranial aneurysm. Child's Nerv Syst. 2009;25(3):317–324. doi:10.1007/s00381-008-0725-2 Fuller AT, Barkley A, Du R, et al. Global neurosurgery: a scoping review detailing the current state of international neurosurgical outreach. J Neurosurg. 2020. doi:10.3171/2020.2.JNS192517 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 15 May, 2026 Reviewers invited by journal 29 Apr, 2026 Editor assigned by journal 18 Mar, 2026 Submission checks completed at journal 18 Mar, 2026 First submitted to journal 16 Mar, 2026 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-9140361","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":632401562,"identity":"86fe33d3-6b6c-4474-a898-c41f14642918","order_by":0,"name":"Oumou Kalsoum Mbacke","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYFACHvYPFQw2DGxA5gEGA5BIAkEtbAxnGNJI13IYWYSAFv4ZucceHNxzPrFP+vjFwwUFdgz87DkGeLVI3MhLNzjw7HZiG19OweEZBskMkj1v8GsxkM4xkP5w4LYxGw9PwmEeA2YGgxsEbAFpkThw4BxMSz2DPRFazIBaDsix8bAfAGo5zGAgQcgv998YGxw4kAzUwsMA1HKcR+LMswK8Wvh7zhg+OHDAjke+h/3xZ54/1XL87ckb8GpBAjxg9/AQqxwE2B+QonoUjIJRMApGEAAAboVEg23PztcAAAAASUVORK5CYII=","orcid":"","institution":"University of Virginia Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Oumou","middleName":"Kalsoum","lastName":"Mbacke","suffix":""},{"id":632401563,"identity":"46a99e30-435b-48e3-916a-8995644ccd4c","order_by":1,"name":"Akaash Suresh","email":"","orcid":"","institution":"University of Virginia Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Akaash","middleName":"","lastName":"Suresh","suffix":""},{"id":632401564,"identity":"ee0d0b70-86d4-446c-b9cf-c3e7334f511f","order_by":2,"name":"Harshit Polavarapu","email":"","orcid":"","institution":"University of Virginia Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Harshit","middleName":"","lastName":"Polavarapu","suffix":""},{"id":632401565,"identity":"7e5c1faf-044b-428c-8eaa-02fb1ada618a","order_by":3,"name":"Omar Thiam","email":"","orcid":"","institution":"Fann Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Omar","middleName":"","lastName":"Thiam","suffix":""},{"id":632401566,"identity":"57aa1e35-6dba-4c0f-89f5-04437a78fb35","order_by":4,"name":"Heather Stevens Spader","email":"","orcid":"","institution":"University of Virginia Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Heather","middleName":"Stevens","lastName":"Spader","suffix":""},{"id":632401567,"identity":"0afaad3c-4ed6-48a5-9e81-63ef3a941295","order_by":5,"name":"Mbaye Thioub","email":"","orcid":"","institution":"Fann Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mbaye","middleName":"","lastName":"Thioub","suffix":""}],"badges":[],"createdAt":"2026-03-16 16:39:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9140361/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9140361/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108957073,"identity":"905c19e3-c18e-4dbd-a029-7fc858760dc3","added_by":"auto","created_at":"2026-05-11 08:16:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24472,"visible":true,"origin":"","legend":"\u003cp\u003eAge distribution by WFNS grade at presentation. Box-and-scatter plot showing age (years) stratified by World Federation of Neurosurgical Societies (WFNS) grade at presentation (Grades 1–4) among 22 pediatric patients with intracranial aneurysms. Boxes represent the interquartile range (IQR), center lines denote medians, whiskers extend to the most extreme values within 1.5 × IQR, and points represent individual patients.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9140361/v1/13b7e8e7c496fed2da752ce0.jpg"},{"id":108957122,"identity":"1cbb5fb8-330f-402f-84f1-046084a84f3c","added_by":"auto","created_at":"2026-05-11 08:16:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33401,"visible":true,"origin":"","legend":"\u003cp\u003eSentinel symptom prevalence by WFNS grade at presentation. Heatmap showing the prevalence of five presenting sentinel symptoms (headache, vomiting, seizures, visual disturbances, altered consciousness) across WFNS grades (1–4) at presentation. Cell values represent the percentage of patients within each WFNS grade exhibiting the symptom.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9140361/v1/645b1c8ed34aea00977c8290.jpg"},{"id":108957128,"identity":"24a4aca6-02d0-4565-b5fe-0ec24a77f857","added_by":"auto","created_at":"2026-05-11 08:16:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":28718,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of admission delay from symptom onset to hospital presentation. Histogram of admission delay (days) from symptom onset to hospital presentation for the study cohort.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9140361/v1/61f3abc75041348e8738054b.jpg"},{"id":108957068,"identity":"0d1b6ec3-a284-4300-8bef-ad360f8e654e","added_by":"auto","created_at":"2026-05-11 08:16:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":27124,"visible":true,"origin":"","legend":"\u003cp\u003eLog-transformed admission delay by WFNS grade at presentation.Scatterplot of log-transformed admission delay (days) versus WFNS grade at presentation (Grades 1–4). Points represent individual patients.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9140361/v1/659e88213802076072fa9325.jpg"},{"id":108957189,"identity":"94d19de6-bf89-4067-ba90-a1ba2b9d8f22","added_by":"auto","created_at":"2026-05-11 08:17:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":300775,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9140361/v1/c0dc097d-b6dd-404e-8a82-e9d9c610c358.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sentinel Symptom Burden and Clinical Severity at Presentation in Pediatric Intracranial Aneurysms: A Retrospective Cohort Study from a Low- and Middle-Income Country","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePediatric intracranial aneurysms (PIAs) are uncommon, accounting for less than 5% of all intracranial aneurysms. The majority of affected children present with ruptured aneurysms and subarachnoid hemorrhage, resulting in significant morbidity.\u0026sup1;\u003csup\u003e\u0026ndash;\u003c/sup\u003e\u0026sup3; These challenges are exacerbated in Low- and Middle-Income Countries (LMICs), where a shortage of neurosurgeons and limited access to diagnostic imaging contribute to delays in diagnosis and intervention.\u003csup\u003e4\u0026ndash;7\u003c/sup\u003e In these situations, frontline providers are often required to make early clinical decisions devoid of immediate access to imaging or specialist consultation, relying solely on clinical assessment to identify high-risk children.\u003c/p\u003e \u003cp\u003eThe World Federation of Neurosurgical Societies (WFNS) grading scale assesses the initial severity of aneurysmal subarachnoid hemorrhage and helps guide urgent care decisions.\u003csup\u003e8,9\u003c/sup\u003e In LMICs, this scale often cannot be used right away, as grading typically waits until after transfer to specialized centers.\u003csup\u003e4,5\u003c/sup\u003e This delay discloses a critical gap: the need for simple, cost-free bedside indicators to help identify children at high risk during early warning symptoms. These symptoms such as sudden severe headache, vomiting, or seizures, may warn of up to 40% of aneurysmal ruptures and can signal minor leaks from unstable aneurysms.\u003csup\u003e10\u003c/sup\u003e While the significance of isolated warning symptoms in adults is debated, the effect of multiple warning signs has not been fully studied.\u003csup\u003e11,12\u003c/sup\u003e Multiple pre-rupture symptoms may mean repeated instability or worsening neurologic involvement. This is especially important in pediatric cases, where symptoms are often unusual, making early recognition harder for general providers.\u003c/p\u003e \u003cp\u003eIn LMIC emergency settings, a simple count of sentinel symptoms may serve as a practical indicator of aneurysmal instability and severity. This study evaluates whether the number of sentinel symptoms is associated with initial WFNS grade in a pediatric intracranial aneurysm cohort from an LMIC.\u003c/p\u003e "},{"header":"METHODS","content":"\n\u003ch3\u003eStudy Design and Setting\u003c/h3\u003e\n\u003cp\u003eThis study was a retrospective observational cohort analysis of pediatric patients with intracranial aneurysms evaluated at a single tertiary referral neurosurgical center in a low- and middle-income country. Patients presenting between January 1, 2013, and December 31, 2024, were eligible for inclusion. Institutional ethics committee approval was obtained, and informed consent was waived due to the retrospective design and use of deidentified data.\u003c/p\u003e \u003cp\u003ePotential cases were identified through a systematic review of institutional neurosurgical logs, inpatient registries, and radiological imaging archives. Patients were managed according to local institutional protocols for suspected intracranial aneurysm and subarachnoid hemorrhage. Clinical variables and timing data were derived from contemporaneous documentation in the electronic medical record.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Identification and Cohort Derivation\u003c/h2\u003e \u003cp\u003eDuring the study period, all pediatric patients with radiologically suspected intracranial aneurysms were screened. Radiological confirmation was established using computed tomography angiography or digital subtraction angiography. Patients were included if they were 18 years of age or younger at presentation and had documented WFNS grade, complete sentinel symptom documentation, and recorded timing from symptom onset to hospital presentation.\u003c/p\u003e \u003cp\u003ePatients were excluded if documentation was insufficient to derive the primary outcome or if prespecified predictors were missing for regression modeling. All eligible consecutive cases during the study period were included without sampling. Regression analyses were performed using complete-case methodology, and the number of observations contributing to each model is reported in the Results. No imputation was performed.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eVariables and Definitions\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was neurological severity at presentation, measured using the World Federation of Neurosurgical Societies (WFNS) grading scale. WFNS grade was abstracted from contemporaneous clinician documentation at the time of initial evaluation and was not retrospectively reassigned. For analysis, WFNS grade was modeled both as an ordinal outcome reflecting ordered severity categories (WFNS grades 1\u0026ndash;4) and as a binary outcome categorized as good-grade (WFNS 1\u0026ndash;2) versus poor-grade (WFNS 3\u0026ndash;4) to enhance clinical interpretability and assess robustness of associations.\u003c/p\u003e \u003cp\u003eThe secondary outcome was radiological severity of subarachnoid hemorrhage measured using the Fisher grading scale on initial computed tomography imaging.\u003c/p\u003e \u003cp\u003eFive sentinel presenting symptoms were abstracted from emergency department and neurosurgical documentation at presentation: headache, vomiting, seizures, visual disturbances, and altered consciousness. Each symptom was coded as present or absent based on physician and nursing documentation. A composite symptom burden score was defined a priori as the total number of sentinel symptoms present at presentation, yielding a range from 0 to 5. Headache was present in all patients and therefore, did not differentiate severity; however, it was retained in descriptive summaries for completeness.\u003c/p\u003e \u003cp\u003eAdmission delay was defined as the time in days from symptom onset to hospital presentation. Because admission delay demonstrated a right-skewed distribution, it was log-transformed using the natural logarithm for regression modeling. Untransformed delay was summarized descriptively to preserve clinical interpretability. Age at presentation was recorded in years and summarized descriptively. Given the cohort size and the rarity of pediatric intracranial aneurysms, regression modeling was limited to the prespecified predictors of symptom burden and log-transformed admission delay to minimize overfitting.\u003c/p\u003e\n\u003ch3\u003eData Collection and Bias Considerations\u003c/h3\u003e\n\u003cp\u003eData were obtained from retrospective review of emergency department records, neurology and neurosurgery consultations, inpatient documentation, and imaging reports. Sentinel symptoms were abstracted from structured fields and narrative notes; when onset timing was unclear, the earliest documented onset was used. Symptom definitions were standardized before abstraction to minimize misclassification. Confounding was addressed by jointly modeling symptom burden and log-transformed admission delay in prespecified regression analyses.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were summarized using medians with ranges or interquartile ranges as appropriate for non-normal distributions. Categorical variables were reported as frequencies and percentages. Descriptive visualizations were generated to illustrate age distribution, symptom clustering across WFNS grades, and patterns of admission delay.\u003c/p\u003e \u003cp\u003eTo evaluate predictors of neurological severity at presentation, an ordinal logistic regression model using the proportional odds framework was fitted with WFNS grade as the ordered dependent variable and symptom burden and log-transformed admission delay as predictors. A secondary binary logistic regression model was fitted using the same predictors, with WFNS grade categorized as good or poor. A separate ordinal logistic regression model was fitted with Fisher grade as the outcome to evaluate associations between symptom burden and radiological hemorrhage severity.\u003c/p\u003e \u003cp\u003eEffect estimates are reported as odds ratios with 95% confidence intervals. Model fit was summarized using McFadden\u0026rsquo;s pseudo-R\u0026sup2;. The proportional odds assumption was evaluated using the Brant test. If the proportional odds assumption was violated, results were interpreted cautiously and compared with the binary logistic regression model. All tests were two-sided, and statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, with interpretation guided primarily by effect estimates and confidence intervals. All analyses were performed using Python statistical libraries.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eClinical Severity at Presentation\u003c/h2\u003e \u003cp\u003eTwenty-two pediatric patients met the inclusion criteria during the study period. WFNS grades at presentation were distributed as follows: Grade 1 in 5 patients (22.7%), Grade 2 in 1 patient (4.5%), Grade 3 in 10 patients (45.5%), and Grade 4 in 6 patients (27.3%). No patient presented with WFNS Grade 5. When dichotomized into good-grade (WFNS 1\u0026ndash;2) and poor-grade (WFNS 3\u0026ndash;4), 6 patients (27.3%) were classified as good-grade and 16 patients (72.7%) as poor-grade.\u003c/p\u003e \u003cp\u003eThe mean age at presentation differed across severity groups. Patients with WFNS 1\u0026ndash;2 had a mean age of approximately 16.8 years, whereas those with WFNS 3\u0026ndash;4 had a mean age of approximately 12.5 years (Mann\u0026ndash;Whitney U test, p\u0026thinsp;\u0026asymp;\u0026thinsp;0.02). Sex distribution did not differ between groups; females comprised 50% of the WFNS 1\u0026ndash;2 group and 56% of the WFNS 3\u0026ndash;4 group (Fisher\u0026rsquo;s exact test, p\u0026thinsp;\u0026gt;\u0026thinsp;0.99).\u003c/p\u003e \u003cp\u003eFunctional status at discharge, measured using the modified Rankin Scale (mRS), was 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 among patients presenting with WFNS 1\u0026ndash;2 and 3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 among those presenting with WFNS 3\u0026ndash;4 (Mann\u0026ndash;Whitney U test, p\u0026thinsp;\u0026asymp;\u0026thinsp;=\u0026thinsp;0.08). Age distribution by WFNS grade is shown in FIG. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003cdiv description=\"image.png\" class=\"Drawing\" id=\"2\" name=\"image1.png\"\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Age distribution by WFNS grade\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSentinel Symptom Burden and WFNS Grade\u003c/h3\u003e\n\u003cp\u003eAll patients (22/22, 100%) reported headache at presentation. Additional presenting symptoms included vomiting in 12 patients (55%), seizures in 7 (32%), altered consciousness in 6 (27%), and visual disturbances in 2 (9%).\u003c/p\u003e \u003cp\u003eThe total number of sentinel symptoms per patient ranged from 1 to 5, with a mean of 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 and a median of 2. Six patients (27%) presented with 1 symptom, 9 (41%) with 2 symptoms, 4 (18%) with 3 symptoms, 2 (9%) with 4 symptoms, and 1 patient (5%) with 5 concurrent symptoms.\u003c/p\u003e \u003cp\u003eAmong patients with WFNS 1\u0026ndash;2 (n\u0026thinsp;=\u0026thinsp;6), vomiting occurred in 3 patients (50.0%) and seizures in 2 (33.3%); none had visual disturbances or altered consciousness. Among patients with WFNS 3\u0026ndash;4 (n\u0026thinsp;=\u0026thinsp;16), vomiting occurred in 9 (56.3%), seizures in 5 (31.3%), visual disturbances in 2 (12.5%), and altered consciousness in 6 (37.5%).\u003c/p\u003e \u003cp\u003eMean symptom count was 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 among patients with WFNS 1\u0026ndash;2 and 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3 among those with WFNS 3\u0026ndash;4. Comparison of symptom counts between groups using the Mann\u0026ndash;Whitney U test yielded U\u0026thinsp;\u0026asymp;\u0026thinsp;37.5 (p\u0026thinsp;\u0026asymp;\u0026thinsp;0.44). Symptom prevalence by WFNS grade is shown in \u003cb\u003eFIG.2.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eAdmission Delay\u003c/h3\u003e\n\u003cp\u003eMean admission delay from symptom onset to hospital presentation was 14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.1 days (range 1\u0026ndash;120 days). The distribution was right-skewed, with a 25th percentile of 1 day, a median of 6.5 days, and a 75th percentile of 9.8 days.\u003c/p\u003e \u003cp\u003eAdmission delay did not differ significantly across individual WFNS grades (1\u0026ndash;4). Comparison using the Kruskal\u0026ndash;Wallis test yielded H\u0026thinsp;\u0026asymp;\u0026thinsp;5.0 (p\u0026thinsp;\u0026asymp;\u0026thinsp;0.17).\u003c/p\u003e \u003cp\u003eWhen WFNS grades were dichotomized, patients with WFNS 1\u0026ndash;2 (n\u0026thinsp;=\u0026thinsp;6) had a mean admission delay of 13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;23.2 days (median 3.5 days), whereas those with WFNS 3\u0026ndash;4 (n\u0026thinsp;=\u0026thinsp;16) had a mean delay of 14.4\u0026thinsp;\u0026plusmn;\u0026thinsp;29.1 days (median 8.5 days). Comparison using the Mann\u0026ndash;Whitney U test yielded U\u0026thinsp;\u0026asymp;\u0026thinsp;42.0 (p\u0026thinsp;\u0026asymp;\u0026thinsp;0.68).\u003c/p\u003e \u003cp\u003eSpearman correlation between WFNS grade (treated as ordinal) and admission delay was ρ \u0026asymp; \u0026minus;0.19 (p\u0026thinsp;\u0026asymp;\u0026thinsp;0.40) on both the raw and log-transformed scales.\u003c/p\u003e \u003cp\u003eAdmission delay distributions are shown in \u003cb\u003eFIG.3\u003c/b\u003e, and the relationship between log-transformed admission delay and WFNS grade is shown in \u003cb\u003eFIG.4\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAcross the cohort, patients presented with a median of 2 sentinel symptoms (range 1\u0026ndash;5). Six patients (27.3%) reported 1 symptom, 9 (40.9%) reported 2 symptoms, 4 (18.2%) reported 3 symptoms, 2 (9.1%) reported 4 symptoms, and 1 patient (4.5%) reported 5 concurrent symptoms.\u003c/p\u003e \u003cp\u003eHeadache was present in all patients (100%) in both the WFNS 1\u0026ndash;2 and WFNS 3\u0026ndash;4 groups. Among patients with WFNS 1\u0026ndash;2, vomiting occurred in 3 of 6 (50.0%) and seizures in 2 of 6 (33.3%); no patient had visual disturbance or altered consciousness. Among patients with WFNS 3\u0026ndash;4, vomiting occurred in 9 of 16 (56.3%), seizures in 5 of 16 (31.3%), visual disturbances in 2 of 16 (12.5%), and altered consciousness in 6 of 16 (37.5%).\u003c/p\u003e \u003cp\u003eIn ordinal logistic regression modeling WFNS grade as an ordered outcome, total presenting symptom count was associated with higher WFNS grade (OR 3.71, 95% CI 1.26\u0026ndash;10.89; p\u0026thinsp;=\u0026thinsp;0.017). Log-transformed admission delay was not associated with WFNS grade (OR 1.12, 95% CI 0.56\u0026ndash;2.26; p\u0026thinsp;=\u0026thinsp;0.75). McFadden\u0026rsquo;s pseudo-R\u0026sup2; for the model was approximately 0.20.\u003c/p\u003e \u003cp\u003eIn binary logistic regression modeling WFNS 3\u0026ndash;4 versus WFNS 1\u0026ndash;2, each additional presenting symptom was associated with an OR of 2.17 (95% CI 0.66\u0026ndash;7.15; p\u0026thinsp;=\u0026thinsp;0.203). Log-transformed admission delay was not associated with binary WFNS status (OR 1.44, 95% CI 0.64\u0026ndash;3.26; p\u0026thinsp;=\u0026thinsp;0.376). McFadden\u0026rsquo;s pseudo-R\u0026sup2; for the binary model was approximately 0.08.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSymptom Burden and Clinical Severity at Presentation\u003c/h2\u003e \u003cp\u003eIn this pediatric cohort, where nearly half of the children presented in poor neurological grade (WFNS 3\u0026ndash;4), the accumulation of sentinel symptoms emerged as a powerful marker of early clinical deterioration. The mean symptom count of 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 indicates that most children arrived with more than one concerning feature, and our data demonstrate a clear gradient: children with three or more symptoms were disproportionately represented among the poor-grade presentations. The multivariable regression confirmed that each additional symptom increased the odds of a higher WFNS grade by nearly fourfold (OR 3.71; 95% CI 1.26\u0026ndash;10.89; p\u0026thinsp;=\u0026thinsp;0.017), a magnitude that carries practical bedside meaning as a single symptom increase nearly quadruples the risk of falling into a worse clinical grade. Children who accumulate\u0026thinsp;\u0026ge;\u0026thinsp;3 symptoms likely represent a clinically significant threshold warranting urgent triage, expedited imaging, or prioritized transfer.\u003csup\u003e8,13\u003c/sup\u003e That symptom count alone explained about 20% of the variance in WFNS grade, underscoring its value as an independent predictor in a population in which traditional markers behaved inconsistently.\u003c/p\u003e \u003cp\u003eEqually important is what did not predict severity. Neither log-transformed admission delay nor Fisher grade significantly correlated with presented WFNS grade in our adjusted analyses, findings that distinguish this pediatric cohort from typical adult SAH patterns.\u003csup\u003e9\u003c/sup\u003e Although the median admission delay was substantial, reflecting well-known LMIC referral challenges, its lack of association with severity indicates that elapsed time from initial symptom to presentation is a poor surrogate for physiological decline in children. Prior pediatric literature has similarly shown that children often deteriorate rapidly and unpredictably, with symptom progression indicating shifts in intracranial dynamics rather than linear temporal decline, suggesting that poor-grade presentation is driven more by acute physiologic changes, such as building intracranial pressure and aneurysm instability, than by delays in presentation.\u003csup\u003e1,2,14,15\u003c/sup\u003e Thus, the cumulative symptom load in our cohort likely captures a physiologic progression from headache to vomiting to seizures, and ultimately to altered mental status, explaining both the nearly fourfold increase in odds of higher WFNS grade per additional symptom and its independence from referral delays.\u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMechanistic Interpretation and Pediatric-Specific Pathophysiology\u003c/h2\u003e \u003cp\u003eThe clustering of symptoms in our cohort\u0026mdash;headache, vomiting, seizures, visual disturbances, and altered consciousness\u0026mdash;maps onto distinct intracranial processes whose cumulative presence plausibly reflects advancing pathophysiology. Headache in pediatric aneurysms is generally attributable to meningeal irritation or acute distention of pain-sensitive vascular structures, while vomiting likely occurs as intracranial pressure increases and brainstem autonomic nuclei are compressed.\u003csup\u003e16,17\u003c/sup\u003e Seizures, which were not uncommon in this series, may have resulted from subcortical involvement and elevated intracranial pressure.\u003csup\u003e15\u003c/sup\u003e Visual complaints may indicate optic pathway compression from giant or fusiform aneurysms, morphologies that are disproportionately represented among pediatric populations compared with adults.\u003csup\u003e18\u003c/sup\u003e Finally, altered consciousness likely reflects global cerebral dysfunction due to impaired perfusion or acute hydrocephalus.\u003csup\u003e14\u003c/sup\u003e The presence of multiple concurrent symptoms in individual patients likely captures escalating physiological compromise and may serve as a practical, clinically relevant triage marker.\u003c/p\u003e \u003cp\u003ePediatric aneurysm biology likely amplifies these relationships. Children exhibit disproportionate rates of giant, fusiform, and dissecting aneurysms with mass-effect-driven presentations far more common than in adults.\u003csup\u003e19\u0026ndash;21\u003c/sup\u003e These features predispose to symptom accumulation even before rupture, and once hemorrhage occurs, the combination of lower cranial compliance and more reactive inflammatory cascades can accelerate clinical deterioration.\u003csup\u003e15\u003c/sup\u003e Prior pediatric SAH work has emphasized that neurological grade correlates more closely with early physiological disruption than with hemorrhage volume, and our data mirror those observations.\u003csup\u003e2,3\u003c/sup\u003e Symptom burden, therefore, appears to integrate these layered physiological stressors into a readily observable clinical signal that may outperform more traditional structural markers in children.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSymptom Count vs. Fisher Grade: Divergence and Implications\u003c/h2\u003e \u003cp\u003eOne of the most striking findings of this study is the limited predictive value of Fisher grade for neurological severity at presentation. In our sample, Fisher grade was not significantly associated with WFNS grade, whereas the model including symptom count accounted for roughly 20% of the variance in presenting severity, representing a considerable improvement in explanatory value. This does not necessarily prove that imaging is intrinsically unreliable in pediatric aneurysms; instead, it may accentuate the likelihood that standard hemorrhage-based grading may fail to capture the full spectrum of pathophysiological variation in children.\u003csup\u003e2,22,23\u003c/sup\u003e Prior pediatric literature documented distinct patterns relative to adults, including a higher prevalence of partially thrombosed aneurysms and a substantial portion of non-ruptured or non-SAH presentations.\u003csup\u003e1,19\u003c/sup\u003e Because such structural and biological heterogeneity may modify how hemorrhage, mass effect, hydrocephalus, and cerebral edema evolve, it is plausible \u0026mdash; though not yet empirically proven \u0026mdash; that static CT-based hemorrhage distribution might underrepresent physiologic compromise in some cases. These unique morphological patterns weaken the reliance on hemorrhage-based grading alone.\u003c/p\u003e \u003cp\u003eIn LMIC contexts such as ours, this discrepancy is further magnified by delays in obtaining CT imaging, interruptions in referral pathways, and variability in initial imaging quality.\u003csup\u003e4,6,7\u003c/sup\u003e When radiologic assessment is delayed by hours to days, hemorrhage redistribution, evolving hydrocephalus, or clot degradation may diminish the reliability of the Fisher grade as an early triage tool.\u003csup\u003e9\u003c/sup\u003e Our findings that Fisher grade did not significantly predict WFNS grade, while simple symptom count did, suggest that clinical features may be more temporally stable and pathophysiologically sensitive indicators of severity in resource-limited settings. This divergence illustrates the potential value of integrating symptom-based approaches into early triage protocols, especially when radiologic severity is unavailable, delayed, or unreliable.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eOptimizing Early Neurosurgical Pathways Through Symptom-Guided Triage\u003c/h2\u003e \u003cp\u003eThe observation that symptom count outperforms both imaging-based and time-based indicators of severity has direct operational implications for structuring early triage and referral processes across diverse neurosurgical systems. A standardized symptom-count field could be incorporated into existing triage forms at first-contact facilities, enabling clinicians to identify high-risk patients even when imaging is delayed or unavailable.\u003csup\u003e13,24\u003c/sup\u003e Similarly, pre-transfer checklists used by ambulance services and regional hospitals could include explicit symptom thresholds that trigger urgent communication with neurosurgical teams, while referral protocols could be designed to prompt consultation when two or more sentinel symptoms are present.\u003csup\u003e6,24\u003c/sup\u003e Evidence from neurosurgery systems research shows that streamlined clinical triggers and simplified referral algorithms can reduce diagnostic delays, improve transfer efficiency, and enhance early decision-making in settings where neurosurgical resources and imaging access vary widely.\u003csup\u003e13\u003c/sup\u003e Within this framework, identifying children with three or more symptoms at the initial point of care could justify bypassing intermediate facilities without neurosurgical capability and expedite transfer to centers capable of definitive management. Prior work in systems strengthening emphasizes that clinical early-warning tools can improve time-to-intervention and reduce preventable neurologic deterioration in both high- and low-resource environments, particularly for time-sensitive neurosurgical emergencies.\u003csup\u003e4,5\u003c/sup\u003e By providing a rapid, no-cost, clinically grounded indicator of physiological compromise, a symptom-based triage approach delivers a practical mechanism for improving referral accuracy, prioritizing limited critical-care capacity, and strengthening the early stages of pediatric aneurysm care pathway.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLIMITATIONS\u003c/h2\u003e \u003cp\u003eThis study must be interpreted within several limitations. First, as a retrospective chart review, all presenting symptoms were abstracted from clinical documentation, which introduces the possibility of underreporting, inconsistent terminology, and variable interpretation among providers, making documentation bias a central limitation of our analysis. Second, we were unable to collect angiographic characteristics such as aneurysm size, morphology, and location. These anatomical features are among the most robust predictors of severity and clinical grade in pediatric aneurysm cohorts, and the absence of these variables limits our ability to adjust for established confounders and to interpret whether symptom burden functions independently of these morphological factors.\u003csup\u003e3,20\u003c/sup\u003e Third, the small sample size of 22 children raises concern about potential model overfitting, particularly given the ratio of predictors to outcomes in the ordinal logistic regression. Although the model demonstrated acceptable stability, the findings should be validated in larger prospective or multicenter datasets.\u003csup\u003e8\u003c/sup\u003e Fourth, because the study was conducted at a single national referral hospital with distinct resource, referral, and documentation constraints, generalizability is limited.\u003csup\u003e4,6\u003c/sup\u003e Symptom-based triage performance may differ in settings with standardized neurological assessments, rapid imaging capacity, or broader availability of pediatric neurosurgical expertise, where faint deficits such as visual changes or early cognitive alterations may be detected more reliably. Finally, our symptom-count metric treats all symptoms equally, although symptoms such as seizures or altered consciousness likely carry greater prognostic importance than headache or vomiting; prospective studies should consider weighted scoring systems and standardized definitions to ensure reproducibility across centers.\u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThese limitations indicate several directions for future work. Larger, prospective cohorts will be essential to validating whether symptom accumulation reliably predicts clinical severity and to determining how predictive effectiveness changes when anatomical variables, such as aneurysm size and morphology, are included. Prospective designs would also allow standardized documentation of sentinel symptoms at first contact, reducing the variability inherent in retrospective note review. Further studies should also evaluate how symptom-guided tools can be operationalized within actual referral networks, as early triage decisions strongly shape outcomes in pediatric neurovascular emergencies.\u003csup\u003e5,13\u003c/sup\u003e Implementation-science approaches, including health-systems modeling, could help determine how such tools might influence transfer timing, neurosurgical service load, ICU utilization, and cost-effectiveness across different health system structures. Together, these steps would advance the development of a practical, scalable early-severity marker that more accurately reflects the unique physiological and systems-level realities of pediatric aneurysm care.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e​\u003c/h2\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this pediatric cohort, accumulation of sentinel symptoms was a meaningful marker of early neurological compromise, outperforming radiographic severity and admission delay in predicting WFNS grade at presentation. Each additional symptom was associated with nearly fourfold higher odds of worse clinical grade, and children with 3 or more symptoms represented a distinct high-risk subgroup, underscoring the dissociation between structural imaging markers and physiological severity in children. A standardized symptom-count metric may offer a pragmatic, accessible triage tool across referral settings, although prospective validation in larger populations is needed to clarify its role alongside established predictors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFUNDING\u003c/h2\u003e \u003cp\u003eThe authors did not receive support from any organization for the submitted work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eO.K.M. contributed to the introduction, discussion, and references and handled the statistics, preparation of figures. A.S and H.P contributed to the introduction, manuscript discussion, and references. O.T was involved in data collection and manuscript review. H.S.S and M.T provided manuscript reviews nd served as senior authors, directing and editing the manuscript throughout. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Fann Teaching Hospital for their partnership and support. We are especially grateful to the individuals involved in data collection for this study. Their contributions were essential to the success of this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSorteberg A, Dahlberg D. Intracranial nontraumatic aneurysms in children and adolescents. Curr Pediatr Rev. 2013;9(4):343–352.\u003c/li\u003e\n\u003cli\u003eHetts SW, Narvid J, Sanai N, Lawton MT, Gupta N, Fullerton HJ, et al. Intracranial aneurysms in childhood: 27-year single-institution experience. AJNR Am J Neuroradiol. 2009;30(7):1315–1324.\u003c/li\u003e\n\u003cli\u003eMeyer FB, Sundt TM Jr, Fode NC, et al. Pediatric intracranial aneurysms: a population-based study. Neurosurgery. 1989;24(4):597–605.\u003c/li\u003e\n\u003cli\u003eWeiss HK, Garcia RM, Omiye JA, Vervoort D, Riestenberg R, Yerneni K, et al. A systematic review of neurosurgical care in low-income countries. World Neurosurg X. 2020;5:100068.\u003c/li\u003e\n\u003cli\u003eFuller A, Tran T, Muhumuza M, Haglund MM. Building neurosurgical capacity in low- and middle-income countries. eNeurologicalSci. 2015;3:1–6.\u003c/li\u003e\n\u003cli\u003eDewan MC, Rattani A, Fieggen G, Arraez MA, Servadei F, Boop FA, et al. Global neurosurgery: workforce density and distribution. J Neurosurg. 2018;130(4):1055–1064.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Medical Imaging Availability in Low-Resource Settings. Geneva, Switzerland: World Health Organization; 2017.\u003c/li\u003e\n\u003cli\u003eNguyen TA, Mai TD, Vu LD, Dao CX, Ngo HM, Hoang HB, et al. Validation of the accuracy of the modified World Federation of Neurosurgical Societies subarachnoid hemorrhage grading scale for predicting outcomes. PLoS One. 2023;18(8):e0289267.\u003c/li\u003e\n\u003cli\u003eLawton MT, Vates GE. Subarachnoid hemorrhage. N Engl J Med. 2017;377(3):257–266.\u003c/li\u003e\n\u003cli\u003eSchievink WI. Intracranial aneurysms. N Engl J Med. 1997;336(1):28–40.\u003c/li\u003e\n\u003cli\u003eBejjani GK, Sakowitz O, Raabe A, et al. Sentinel headache and the risk of rebleeding after aneurysmal subarachnoid hemorrhage. Stroke. 2006;37(11):2733–2737.\u003c/li\u003e\n\u003cli\u003eViarasilpa T, Chou SHY, Chou SH, Kawai K, et al. Prognostic significance of sentinel headache preceding aneurysmal subarachnoid hemorrhage. World Neurosurg. 2020;139:e672-e676.\u003c/li\u003e\n\u003cli\u003eSchnurman Z, Chin R, Fishkin ER, Huang PP. Maximizing interhospital transfer resources for neurosurgical patients. World Neurosurg. 2017;104:702–708. doi:10.1016/j.wneu.2017.05.082\u003c/li\u003e\n\u003cli\u003eAddis A, Baggiani M, Citerio G. Intracranial pressure monitoring and management in aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2023;39(1):59–69. doi:10.1007/s12028-023-01752-y\u003c/li\u003e\n\u003cli\u003eRass V, Helbok R. Early brain injury after poor-grade subarachnoid hemorrhage. Curr Neurol Neurosci Rep. 2019;19(10):78. doi:10.1007/s11910-019-0990-3\u003c/li\u003e\n\u003cli\u003eMarcolini E, Hine J. Approach to the diagnosis and management of subarachnoid hemorrhage. West J Emerg Med. 2019;20(2):203–211. doi:10.5811/westjem.2019.1.37352\u003c/li\u003e\n\u003cli\u003eWelty TE, Horner TG. Pathophysiology and treatment of subarachnoid hemorrhage. Clin Pharm. 1990;9(1):35–39.\u003c/li\u003e\n\u003cli\u003ede Oliveira JG, Borba LA, Rassi-Neto A, et al. Intracranial aneurysms presenting with mass effect over the anterior optic pathways: neurosurgical management and outcomes. Neurosurg Focus. 2009;26(5):E3. doi:10.3171/2009.3.FOCUS0924\u003c/li\u003e\n\u003cli\u003eBrandel MG, Plonsker JH, Rennert RC, et al. Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review. Child's Nerv Syst. 2024;40(8):2419–2429. doi:10.1007/s00381-024-06384-x\u003c/li\u003e\n\u003cli\u003eGupta S, Hauser BM, Catapano JS, et al. Rupture risk and outcomes of giant aneurysms in pediatric patients: a multi-institutional case series and systematic review. J Neurosurg Pediatr. 2023;33(3):276–284. doi:10.3171/2023.10.PEDS23296\u003c/li\u003e\n\u003cli\u003eLevy ML, Levy DM, Manna B. Pediatric cerebral aneurysm. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023.\u003c/li\u003e\n\u003cli\u003ede Aguiar GB, Ozanne A, Elawady A, et al. Intracranial aneurysm in the pediatric population: a single-center experience. Pediatr Neurosurg. 2022;57(4):270–278. doi:10.1159/000524523\u003c/li\u003e\n\u003cli\u003eLiang J, Bao Y, Zhang H, et al. Clinical features and treatment of pediatric intracranial aneurysm. Child's Nerv Syst. 2009;25(3):317–324. doi:10.1007/s00381-008-0725-2\u003c/li\u003e\n\u003cli\u003eFuller AT, Barkley A, Du R, et al. Global neurosurgery: a scoping review detailing the current state of international neurosurgical outreach. J Neurosurg. 2020. doi:10.3171/2020.2.JNS192517\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatric intracranial aneurysm, Sentinel symptoms, WFNS grade, Fisher grade, Clinical severity, Triage, Low- and middle-income countries, Global neurosurgery","lastPublishedDoi":"10.21203/rs.3.rs-9140361/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9140361/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eINTRODUCTION\u003c/p\u003e\n\u003cp\u003eIn low- and middle-income countries (LMICs), early bedside assessment is critical for informing triage decisions when imaging and subspecialty care are limited. The present study evaluated whether the burden of presenting sentinel symptoms is associated with clinical severity at presentation among pediatric patients with intracranial aneurysms.\u003c/p\u003e\n\u003cp\u003eMETHODS\u003c/p\u003e\n\u003cp\u003eA retrospective analysis was performed on 22 pediatric patients (≤ 18 years) with radiologically confirmed intracranial aneurysms treated at a tertiary LMIC center between 2013 and 2024. Five presenting sentinel symptoms such as headache, vomiting, seizures, visual disturbances, and altered consciousness, were collected from clinical records, and symptom burden was defined as the total symptom count (0–5). The primary outcomes were WFNS grade and Fisher grade at presentation. Ordinal logistic regression was used to model the association between symptom count and WFNS grade, adjusting for log-transformed admission delay.\u003c/p\u003e\n\u003cp\u003eRESULTS\u003c/p\u003e\n\u003cp\u003eThe mean age of the cohort was 13.3 ± 4.9 years. Presenting symptoms included headache in all patients (100%), vomiting in 12 (55%), seizures in 7 (32%), altered consciousness in 6 (27%), and visual disturbances in 2 (9%). Patients presented with 1 to 5 sentinel symptoms (mean 2.4 ± 1.2). WFNS grades at presentation were distributed as follows: Grade 1 in 5 patients (23%), Grade 2 in 1 patient (5%), Grade 3 in 10 patients (45%), and Grade 4 in 6 patients (27%). Ordinal logistic regression demonstrated that each additional presenting symptom was associated with a higher WFNS grade (OR 3.71, 95% CI 1.26–10.89; p = 0.017), with McFadden’s pseudo-R² approximately 0.20. Fisher grade was not associated with WFNS grade (p = 0.140). Admission delay averaged 14.0 ± 27.1 days (range 1–120), and log-transformed admission delay was not associated with WFNS grade (OR 1.12, 95% CI 0.56–2.26; p = 0.750).\u003c/p\u003e\n\u003cp\u003eCONCLUSION\u003c/p\u003e\n\u003cp\u003eIn this cohort, a higher burden of presenting sentinel symptoms was associated with increased WFNS grade at presentation. These findings support further evaluation of symptom count as a clinical marker of initial neurological severity in pediatric intracranial aneurysms, particularly within resource-limited settings.\u003c/p\u003e","manuscriptTitle":"Sentinel Symptom Burden and Clinical Severity at Presentation in Pediatric Intracranial Aneurysms: A Retrospective Cohort Study from a Low- and Middle-Income Country","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 08:15:15","doi":"10.21203/rs.3.rs-9140361/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"208910383390090889538921835969337341706","date":"2026-05-15T11:15:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-29T12:10:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-18T05:55:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-18T05:54:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"Child's Nervous System","date":"2026-03-16T16:24:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"95ec801a-0a73-49e9-a726-ba22af9829b2","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"208910383390090889538921835969337341706","date":"2026-05-15T11:15:28+00:00","index":15,"fulltext":""},{"type":"reviewersInvited","content":"7","date":"2026-04-29T12:10:17+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T08:15:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 08:15:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9140361","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9140361","identity":"rs-9140361","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}