Evaluation of the Combined Use of Optic Nerve Sheath Diameter and the FOUR Score in Predicting Brain Death in Patients with Severe Brain Injury Admitted to the Intensive Care Unit

Evaluation of the Combined Use of Optic Nerve Sheath Diameter and the FOUR Score in Predicting Brain Death in Patients with Severe Brain Injury Admitted to the Intensive Care Unit | 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 Evaluation of the Combined Use of Optic Nerve Sheath Diameter and the FOUR Score in Predicting Brain Death in Patients with Severe Brain Injury Admitted to the Intensive Care Unit Eralp Çevikkalp, Gülbahar Çalışkan, Emre Ulusoy This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8732205/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Brain death is a catastrophic outcome of severe brain injury, most commonly associated with progressive intracranial hypertension. Early identification of patients at risk for brain death remains challenging. Optic nerve sheath diameter (ONSD), reflecting intracranial pressure, and the Full Outline of UnResponsiveness (FOUR) score, assessing neurological function, have been proposed as prognostic tools; however, evidence regarding their combined use is limited. Objective To evaluate the predictive value of ONSD and the FOUR score, individually and in combination, for the development of brain death in patients admitted to the intensive care unit with severe brain injury. Methods This single-center, retrospective study included adult patients with severe neurological impairment (Glasgow Coma Scale ≤ 7). ONSD was measured on admission cranial computed tomography scans. Clinical data and neurological scores were recorded. A modified FOUR score incorporating ONSD as a fifth parameter was developed. The primary outcome was the development of brain death during intensive care follow-up. Results Among 316 patients, those who developed brain death had significantly lower GCS and FOUR scores and significantly higher ONSD values (p 5.62 mm demonstrated excellent discriminative performance for predicting brain death (AUC: 0.992; sensitivity 98.65%, specificity 97.52%). The modified FOUR score showed high sensitivity but limited specificity, suggesting a screening rather than a definitive discriminative role. In multivariable analysis, ONSD was the only independent predictor of brain death (OR: 345.7; p < 0.001). Conclusions ONSD is a strong and independent predictor of brain death in patients with severe brain injury. While the FOUR score provides valuable clinical information, its prognostic utility appears enhanced when combined with objective markers of intracranial hypertension. The modified FOUR score may serve as a complementary screening tool, whereas ONSD offers robust discriminatory power. Integrating clinical neurological assessment with imaging-based parameters may improve early risk stratification for brain death. Optic nerve sheath diameter Brain death FOUR score Severe brain injury Neurocritical care Figures Figure 1 Figure 2 INTRODUCTION Brain death is a condition characterized by the irreversible loss of all brain functions and has important clinical and legal implications [ 1 ]. Patients admitted to the intensive care unit who have a Glasgow Coma Scale (GCS) score of 3, absence of at least three brainstem reflexes, or a Full Outline of UnResponsiveness (FOUR) score of 0, and who are deeply comatose due to irreversible brain injury while receiving mechanical ventilation, are defined as having “imminent brain death” in terms of potential organ donation [ 2 ]. Rapid and progressive increases in intracranial pressure (ICP) resulting from severe brain injury constitute one of the key pathophysiological steps leading to brain death [ 3 ]. Elevated ICP results in impaired cerebral perfusion, loss of brainstem function, and ultimately global cerebral ischemia. Therefore, early and reliable detection of ICP elevation in patients with severe brain injury plays a critical role in predicting clinical course and outcomes [ 4 ]. Although invasive monitoring methods are considered the gold standard for the assessment of intracranial pressure, interest in noninvasive, easily applicable, and repeatable techniques has increased. The optic nerve sheath, as an extension of the dura mater and due to its direct anatomical connection with the subarachnoid space, has emerged as a structure that reflects changes in intracranial pressure. Numerous studies have reported that measurements of optic nerve sheath diameter (ONSD) show a significant correlation with elevated intracranial pressure and are associated with poor neurological outcomes (5–6). Previous studies have shown that ONSD values above 5.5 mm correlate with intracranial hypertension, whereas ONSD measurements greater than 6.62 mm are predictive of brain death development [ 7 , 8 ]. Clinical neurological scoring systems are widely used to assess the functional impact of brain injury. The FOUR score, which includes brainstem reflexes and respiratory pattern, provides a more comprehensive clinical evaluation than the GCS, particularly in intubated intensive care unit patients (9,10). Although low FOUR scores have been associated with increased mortality and poor neurological outcomes, this score does not include an objective measure that directly reflects intracranial pressure elevation [ 10 , 11 ]. While previous studies have evaluated the prognostic value of optic nerve sheath diameter and the FOUR score separately, studies that directly address the development of brain death as an outcome and assess these two parameters together in patients followed in the intensive care unit due to severe brain injury are limited [ 8 , 10 , 11 ]. The combined evaluation of clinical neurological findings and an imaging-based parameter reflecting intracranial pressure elevation may contribute to earlier and more accurate identification of patients at high risk for developing brain death. In this study, we aimed to evaluate the role of optic nerve sheath diameter measured at admission and the FOUR score in predicting the development of brain death in patients with severe neurological injury followed in the intensive care unit due to severe brain injury. In addition, we sought to determine the potential contribution of the combined use of these two parameters in discriminating the development of brain death. METHODOLOGY Study Design and Patient Selection This single-center, retrospective study was conducted to evaluate the role of optic nerve sheath diameter (ONSD) and the FOUR score in predicting the development of brain death in patients admitted to the intensive care unit due to diffuse brain injury (hemorrhage, ischemia, hypoxia, etc.). The study was carried out in the Anesthesiology and Reanimation Intensive Care Units of Bursa City Hospital. Patients aged 18 years and older who were admitted to the intensive care unit from the emergency department, had a GCS score of 7 or less, were followed with a diagnosis of severe acute brain injury, were not operated on, and were under mechanical ventilation support were included in the study. Patients younger than 18 years, those with neurological disorders secondary to intoxication, hypercapnia, or sepsis, patients who had undergone decompression surgery, those with maxillofacial trauma or skull base fractures, patients followed in the intensive care unit for less than 24 hours, and patients without cranial computed tomography (CT) evaluation in the emergency department were excluded. Data Collection Demographic characteristics (age, sex), indications for intensive care unit admission, comorbidities, and clinical scores (GCS, FOUR score, and Acute Physiology and Chronic Health Evaluation [APACHE] II score) were retrospectively recorded from patient files and electronic medical records. GCS and FOUR scores were determined based on clinical assessment at the time of intensive care unit admission. The Glasgow Coma Scale (GCS), Full Outline of UnResponsiveness (FOUR) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score applied in this study are previously established and validated clinical scoring systems, and were not developed specifically for this research. The original publications describing these scales have been cited accordingly[9,22,23]. In addition, a modified FOUR score incorporating optic nerve sheath diameter (ONSD) as an additional parameter was developed for exploratory purposes in the present study. This modified score was designed to assess the potential complementary value of ONSD and has not been externally validated. The scoring system is presented in Supplementary Table 1. Optic Nerve Sheath Diameter Measurement Optic nerve sheath diameter measurements were performed using cranial computed tomography images obtained at the time of intensive care unit admission. Measurements were made for both eyes, 3 mm posterior to the globe, on transverse sections, and recorded in millimeters [8]. All optic nerve sheath diameter measurements were performed by a single experienced physician in order to minimize measurement variability. Interobserver reliability analysis could not be performed due to the retrospective design of the study. Optic nerve sheath diameter values were additionally categorized and scored in accordance with the literature and used in the analyses. Modified FOUR Score To evaluate the value added by ONSD to the FOUR score, a modified FOUR score has been developed. ONSD has been added as the 5th parameter to the FOUR score. The literature reports that ONSD is up to 4.0 mm in children younger than 1 year, 4.5 mm in those aged 1-18 years, and 5.0 mm in adults [5,6]. In patients followed up for subarachnoid hemorrhage, an ONSD measurement higher than 5.5 mm has been shown to significantly indicate high intracranial pressure [7]. In the study by Çevikalp et al., it was determined that an ONSD above 6.62 mm is a cut-off value for predicting brain death. Based on these studies, the scoring system outlined in Table 1 was developed. The modified FOUR score was developed for exploratory purposes and was not intended to replace the original FOUR score or to serve as a validated diagnostic tool. Outcome Measure The primary outcome of the study was the development of brain death during intensive care unit follow-up. During follow-up, patients were categorized into two groups: those who developed brain death (BD group) and those who did not develop brain death (non-BD group), and clinical, radiological, and score-based variables were compared between the groups. Brain Death Determination Process In Türkiye, the framework for brain death determination is defined by national legislation and regulations [1]. According to these regulations, brain death is defined as the permanent and irreversible loss of all functions of the brain, brainstem, and cerebellum. For the diagnosis of brain death, after identifying the structural cause leading to brain injury and excluding reversible conditions, the presence of deep coma, absence of brainstem reflexes, and a positive apnea test must be demonstrated clinically. In addition, confirmation that the state of deep coma persists after the legally mandated observation period is required to establish the diagnosis of brain death. When a confirmatory test assessing cerebral circulation is used for diagnosis, the absence of blood flow in all intracerebral arteries and their branches is required. Results A total of 316 patients admitted to the intensive care unit due to severe brain injury were included in the study (Figure 1). The mean age of the cohort was 59.37±20.86 years, and 63.9% were male. During follow-up, patients were categorized into two groups: those who developed brain death ( BD group ) and those who did not ( non-BD group ). The non-BD group was significantly older than the BD group (60.44 ± 21.55 vs 55.86 ± 18.27 years, p = 0.016). Sex distribution did not differ between groups (p = 0.891). (Table 2). APACHE II scores were similar between groups (p = 0.086). In contrast, neurological scores were significantly lower in the BD group, with both GCS and FOUR scores showing marked differences compared with the non-BD group (p < 0.001 for both). Length of ICU stay was significantly longer in the non-BD group (30.55 ± 24.66 vs 8.38 ± 6.20 days, p < 0.001) (Table 2). Optic Nerve Sheath Diameter Optic nerve sheath diameter was significantly higher in the BD group (6.30 ± 0.50 mm) compared with the non-BD group (4.38 ± 0.61 mm, p < 0.001). While transverse diameter did not differ between groups (p = 0.194), the optic nerve–to–transverse diameter ratio was significantly higher in the BD group (0.28 ± 0.03 vs 0.20 ± 0.03, p 5.62 mm yielding a sensitivity of 98.65% and a specificity of 97.52% (AUC: 0.992 , 95% CI: 0.975–0.999; p < 0.001) (Figure 2). In contrast, the modified FOUR score showed high sensitivity but limited specificity at a cut-off value of ≤9 (93.24% sensitivity, 34.71% specificity; AUC: 0.591 , p = 0.007) (Table 3)( Figure 2). In multivariable logistic regression analysis, including demographic, clinical, and radiological variables, ONSD was the only independent predictor of brain death development. Each 1-mm increase in ONSD was associated with a 345.7-fold increase in the risk of brain death (OR: 345.7; 95% CI: 36.6–3266.7; p < 0.001). The model explained 91.1% of outcome variability (Table 4). DISCUSSION This study demonstrated significant associations between the development of brain death and both clinical neurological scores and imaging-derived parameters in patients with severe brain injury monitored in the intensive care unit. Patients who progressed to brain death exhibited significantly lower FOUR and GCS scores, alongside significantly higher ONSD and optic nerve–to–transverse diameter ratios. Considering the results of ROC and multivariate analyses, ONSD emerged as a strong and independent predictor of brain death. In contrast, the FOUR score showed high sensitivity but limited overall discriminatory ability. Collectively, these findings indicate that integrating clinical neurological assessments with objective imaging markers of elevated intracranial pressure may enhance prognostic accuracy in this critically ill population. The FOUR score was developed to provide a more comprehensive clinical assessment than the GCS, particularly in mechanically ventilated patients in the intensive care unit, as it incorporates eye response, motor response, brainstem reflexes, and respiratory pattern (9). Previous studies have demonstrated an association between lower FOUR scores and increased mortality, as well as poorer neurological outcomes. In addition, when compared to the GCS, it may offer greater accuracy in predicting short-term mortality in certain intensive care populations [ 9 – 11 ]. Nevertheless, the FOUR score remains a functional assessment based on clinical examination and does not incorporate objective measures that directly reflect underlying pathophysiological processes, such as elevated intracranial pressure. The optic nerve sheath is susceptible to changes in intracranial pressure because it is anatomically continuous with the subarachnoid space. When intracranial pressure increases, the transmission of cerebrospinal fluid to the optic nerve sheath results in a measurable expansion of its diameter [ 12 ]. Numerous studies have demonstrated that ONSD measurements correlate significantly with invasive intracranial pressure monitoring and are associated with increased mortality and poor neurological outcomes [ 13 – 18 ]. Thus, these findings support the role of optic nerve sheath diameter as an objective marker of intracranial hypertension with potential value in prognostic assessment. Although most studies evaluating optic nerve sheath diameter have used ultrasonography, computed tomography–based measurements offer higher anatomical resolution and are less operator-dependent. In the present study, CT-based ONSD assessment provided a standardized and reproducible approach in a retrospective intensive care cohort. Although the relevant studies in the literature have demonstrated associations between increased ONSD, elevated intracranial pressure, catastrophic brain injury, and poor neurological outcomes, investigations that specifically evaluate brain death as an endpoint remain limited [ 19 – 21 ]. Among the few studies addressing this issue, Çevikkalp et al. reported an ONSD threshold of 6.62 mm for predicting the development of brain death in patients monitored for intracranial hemorrhage [ 8 ]. In the present study, a lower cut-off value (> 5.62 mm) showed strong discriminatory performance, with high sensitivity and specificity for predicting brain death. This discrepancy may be attributable to differences in study design and patient populations. Previous research in neuro–intensive care settings has suggested that ultrasonography-based ONSD measurements can serve as a complementary tool in prognostic assessment [ 18 ]. Similarly, studies using computed tomography have shown that increased ONSD values non-invasively reflect dynamic changes in intracranial pressure and may indicate advanced cerebral injury [ 19 , 21 ]. Moreover, a recent systematic review and meta-analysis by Xu et al. confirmed that ONSD is a reliable non-invasive marker of intracranial hypertension in traumatic brain injury [ 19 ]. Taken together, these findings support the consideration of ONSD as a valuable prognostic marker in the progression toward brain death in patients with severe brain injury. In this study, the observation of significantly lower FOUR scores alongside significantly higher ONSD and optic nerve–to–transverse diameter ratios in patients who developed brain death indicates that optic nerve sheath diameter is a critical parameter with prognostic, as well as diagnostic, significance. The identification of ONSD as an independent predictor in multivariate analyses further underscores the central role of elevated intracranial pressure in the pathophysiological process leading to brain death. ROC analysis demonstrated that a modified FOUR score cut-off value of ≤ 9 yielded high sensitivity (93.24%) but low specificity (34.71%). This pattern suggests that the modified FOUR score functions effectively as a screening tool for identifying patients at risk of developing brain death, while having limited ability to discriminate those who will not progress to this outcome. Given that the FOUR score is a clinically based scale reflecting early and relatively non-specific manifestations of severe neurological injury, its high sensitivity coupled with low specificity is not unexpected. Moreover, in the national clinical context, the diagnosis of brain death is defined by the irreversible loss of all brain functions, including the brain, brainstem, and cerebellum, and is frequently supported by confirmatory tests assessing cerebral circulation. This diagnostic framework may further limit the discriminatory capacity of the FOUR score, as it does not directly assess the complete cessation of global cerebral blood flow. Consequently, some patients with profound clinical neurological impairment and low FOUR scores may not yet fulfill the formal diagnostic criteria for brain death. It should be emphasized that the modified FOUR score proposed in this study has not been externally validated and should be interpreted as an exploratory screening tool rather than a definitive prognostic model. In contrast, in the present study, ONSD emerged as a robust objective predictor of brain death, demonstrated by its high discriminatory performance in ROC analysis and its identification as an independent predictor in multivariate analysis. The combined interpretation of these analyses indicates that the modified FOUR score alone lacks sufficient diagnostic accuracy; however, when integrated with an objective, pathophysiologically grounded measure such as ONSD, it may serve as a complementary clinical tool that facilitates the early identification of patients at high risk of progressing to brain death. This study has several limitations. Its single-center, observational design limits the generalizability of the findings. The relatively small sample size precluded detailed subgroup analyses, and the assessment of ONSD at a single time point did not allow evaluation of dynamic changes in intracranial pressure over time. Optic nerve sheath diameter was assessed at a single time point using computed tomography, which did not allow evaluation of dynamic intracranial pressure changes or interobserver variability. Additionally, brain death was diagnosed using clinical criteria and ancillary tests, and it was not possible to control for all potential confounding factors. The modified FOUR score introduced in this study has not undergone external validation, which limits its generalizability. In conclusion, ONSD emerged as a strong and independent predictor of brain death in patients admitted to the intensive care unit due to severe brain injury. The integration of clinical neurological assessments with objective indicators of intracranial pressure may facilitate the early identification of patients at high risk for brain death. To more clearly establish the clinical utility of this combined approach, prospective, multicenter studies with brain death as the primary endpoint are warranted. Abbreviations GCS: Glasgow Coma Scale FOUR: Full Outline of UnResponsiveness ONSD: Optic Nerve Sheath Diameter ICU: Intensive Care Unit APACHE II: Acute Physiology and Chronic Health Evaluation II Declarations Ethics approval and consent to participate This study was approved by the Bursa City Hospital Ethics Committee and conducted in accordance with the Declaration of Helsinki. Due to the retrospective nature of the study, the requirement for informed consent was waived. Consent for publication Written informed consent for publication was obtained from the patient or their legal representatives. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no financial support for the research, authorship, and/or publication of this article. Authors’ contributions EÇ conceived and designed the study. GÇ collected the data. EU performed the statistical analysis. All authors interpreted the data, drafted the manuscript, and approved the final version. Acknowledgements Not applicable. References Arsava EM, Ünal A. Turkish Neurological Society Diagnostic Guidelines for Brain Death*. De Groot YJ, Jansen NE, Bakker J, Kuiper MA, Aerdts S, Maas AIR, et al. Imminent brain death: point of departure for potential heart-beating organ donor recognition. Intensive Care Med. 2010;36(9):1488–94. Salih F, Holtkamp M, Brandt SA, Hoffmann O, Masuhr F, Schreiber S, et al. Intracranial pressure and cerebral perfusion pressure in patients developing brain death. J Crit Care. 2016;34:1–6. Le Roux P, Menon DK, Citerio G, Vespa P, Bader MK, Brophy GM et al. 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Comparison of demographic, clinical, and radiological characteristics between groups Variable Brain Death Intracranial hemorrhage p value Sex Female 26 (35.1%) 88 (36.4%) 0.891 a Male 48 (64.9%) 154 (63.6%) Diagnosis Subarachnoid hemorrhage 30 (40.5%) 85 (35.1%) 0.009 b Parenchymal hemorrhage 19 (25.7%) 90 (37.2%) Intraventricular hemorrhage 20 (27.0%) 43 (17.8%) Ischemia 0 (0%) 17 (7.0%) Hypoxia 4 (5.4%) 4 (1.7%) Pons hemorrhage 1 (1.4%) 3 (1.2%) Hypertension 33 (44.6%) 97 (40.1%) 0.490 a Comorbidities Diabetes mellitus 14 (18.9%) 68 (28.1%) 0.154 c Coronary artery disease 14 (18.9%) 27 (11.2%) 0.123 c Cerebrovascular disease 12 (16.2%) 40 (16.6%) 1.000 c Chronic obstructive pulmonary disease 2 (2.7%) 13 (5.4%) 0.534 d Malignancy 2 (2.7%) 28 (11.6%) 0.040 b Other 20 (27.0%) 119 (49.2%) 0.001 a Age 55.86 ± 18.27 57 (4 - 84) 60.44 ± 21.55 66 (0 - 95) 0.016 e Optic nerve sheath diameter (mm) 6.30 ± 0.50 6.33 (5.38 – 7.76) 4.38 ± 0.61 4.35 (3.14 – 6.68) <0.001 e Transverse diameter (mm) 22.32 ± 1.11 22.19 (19.20 – 25.21) 22.48 ± 0.99 22.42 (19.76 – 25.21) 0.194 e ONSD / Transverse diameter ratio 0.28 ± 0.03 0.28 (0.22 – 0.37) 0.20 ± 0.03 0.20 (0.14 – 0.31) <0.001 e Days 8.38 ± 6.20 6 (2 - 25) 30.55 ± 24.66 24.5 (2 - 96) <0.001 e APACHE score 19.18 ± 8.06 20.5 (3 - 36) 18.31 ± 8.69 18.0 (0 - 47) 0.086 a GCS score 4.54 ± 1.56 4 (3 - 8) 5.84 ± 2.06 6 (3 - 10) <0.001 a FOUR score 3.35 ± 3.17 2 (0 – 12) 6.39 ± 4.12 6 (0 – 16) <0.001 a a Pearson chi-square test; b Fisher–Freeman–Halton chi-square test; c Yates’ chi-square test; d Fisher’s exact test; e Mann–Whitney U test ONSD , optic nerve sheath diameter; GCS , Glasgow Coma Scale; FOUR , Full Outline of UnResponsiveness; APACHE , Acute Physiology and Chronic Health Evaluation. Table 3. ROC analysis results for predicting brain death Cut-off Youden Index AUC (%95 CI) Sensitivity (%95 CI) Specificity (%95 CI) p-value ONSD >5.62 0.9617 0.992 (0.975 – 0.999) 98.65 (92.7 – 100.0) 97.52 (94.7 – 99.1) <0.001 a mFOUR ≤9 0.2795 0.591 (0.534 – 0.645) 93.24 (84.9 – 97.8) 34.71 (28.7 – 41.1) 0.007 a a ROC Analysis ONSD , optic nerve sheath diameter; mFOUR , modified Full Outline of UnResponsiveness; AUC , area under the curve; CI , confidence interval. Dependent variable: Development of brain death Independent variables: Age, GCS, modified FOUR score, transverse diameter, optic nerve sheath diameter Table 4. Multivariate logistic regression analysis for predictors of brain death B Standard Error Wald df p Exp(B) %95 CI Days -0.085 0.037 5.21 1 0.022 0.919 0.854 – 0.988 ONSD 5.846 1.146 26.03 1 <0.001 345.7 36.6 – 3266.7 Constant -31.689 6.445 24.18 1 <0.001 Model explanatory power: 91.1% Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 02 May, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers invited by journal 17 Feb, 2026 Editor assigned by journal 14 Feb, 2026 Editor invited by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 04 Feb, 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-8732205","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":592910960,"identity":"9eb11d97-3fd9-4cfe-853e-f57dccab3265","order_by":0,"name":"Eralp Çevikkalp","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIie3PMWrDMBSA4RcC8iKjrSgE4iuoZMlg0qvoEfDWYujSIYMhoKUhXRt6iRRDyGgQaHLbtcWLoRdwN2+t1UCy2KZjB/2DEEIfTwJwuf5ng8yuhBKAEkL5eybjfnMmEiIJxBLxBwJHoo8Eeggb61LHyxA31GCFh7cbFtxjVQoI2EXWSkabSOhHE6HyleaYF7cj5ae8edjl9km2EpGD0H6ip4R5CUdV4M74O0ukKNrJVe5VDfm2ZFWjerUkrfuIoNROySbEV6aZklmy753Ccxo3f1lMCDXRDPMFbtX1fiYF7/wLW3vPn/FyToN1NH3/OszxYfiSftR3YcDG7cQ2PO0GyXl85/VO4nK5XK5TP47xX92tvnU1AAAAAElFTkSuQmCC","orcid":"","institution":"Ministry of Health","correspondingAuthor":true,"prefix":"","firstName":"Eralp","middleName":"","lastName":"Çevikkalp","suffix":""},{"id":592910961,"identity":"81cdd57c-2f6a-45a3-bd2e-c3688244a960","order_by":1,"name":"Gülbahar Çalışkan","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Gülbahar","middleName":"","lastName":"Çalışkan","suffix":""},{"id":592910962,"identity":"51198b3e-8df3-4f2b-933d-95e449b5324d","order_by":2,"name":"Emre Ulusoy","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Emre","middleName":"","lastName":"Ulusoy","suffix":""}],"badges":[],"createdAt":"2026-01-29 13:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8732205/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8732205/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103176305,"identity":"4735382b-ce98-4fcb-bbfc-9f36f73e4668","added_by":"auto","created_at":"2026-02-22 16:35:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54107,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8732205/v1/22b36bcb8ec82c260372ab40.png"},{"id":103176306,"identity":"cfdfe82d-9ba8-4786-b94a-af69ffefdcbf","added_by":"auto","created_at":"2026-02-22 16:35:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":397097,"visible":true,"origin":"","legend":"\u003cp\u003eROC Analyses\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8732205/v1/d0ef23ca02e9639efedac50b.png"},{"id":103504446,"identity":"1512330a-4149-432d-ab0c-8ffc16dac66b","added_by":"auto","created_at":"2026-02-26 13:19:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1565238,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8732205/v1/cf86e8ae-8f03-4e1d-bdf7-9de5327b945b.pdf"},{"id":103176307,"identity":"37f3833e-b90c-495f-96d1-006c0adcc33a","added_by":"auto","created_at":"2026-02-22 16:35:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13135,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8732205/v1/07986e3c1e7361b7c4c937c8.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of the Combined Use of Optic Nerve Sheath Diameter and the FOUR Score in Predicting Brain Death in Patients with Severe Brain Injury Admitted to the Intensive Care Unit","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBrain death is a condition characterized by the irreversible loss of all brain functions and has important clinical and legal implications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Patients admitted to the intensive care unit who have a Glasgow Coma Scale (GCS) score of 3, absence of at least three brainstem reflexes, or a Full Outline of UnResponsiveness (FOUR) score of 0, and who are deeply comatose due to irreversible brain injury while receiving mechanical ventilation, are defined as having \u0026ldquo;imminent brain death\u0026rdquo; in terms of potential organ donation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRapid and progressive increases in intracranial pressure (ICP) resulting from severe brain injury constitute one of the key pathophysiological steps leading to brain death [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Elevated ICP results in impaired cerebral perfusion, loss of brainstem function, and ultimately global cerebral ischemia. Therefore, early and reliable detection of ICP elevation in patients with severe brain injury plays a critical role in predicting clinical course and outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough invasive monitoring methods are considered the gold standard for the assessment of intracranial pressure, interest in noninvasive, easily applicable, and repeatable techniques has increased. The optic nerve sheath, as an extension of the dura mater and due to its direct anatomical connection with the subarachnoid space, has emerged as a structure that reflects changes in intracranial pressure. Numerous studies have reported that measurements of optic nerve sheath diameter (ONSD) show a significant correlation with elevated intracranial pressure and are associated with poor neurological outcomes (5\u0026ndash;6). Previous studies have shown that ONSD values above 5.5 mm correlate with intracranial hypertension, whereas ONSD measurements greater than 6.62 mm are predictive of brain death development [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinical neurological scoring systems are widely used to assess the functional impact of brain injury. The FOUR score, which includes brainstem reflexes and respiratory pattern, provides a more comprehensive clinical evaluation than the GCS, particularly in intubated intensive care unit patients (9,10). Although low FOUR scores have been associated with increased mortality and poor neurological outcomes, this score does not include an objective measure that directly reflects intracranial pressure elevation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile previous studies have evaluated the prognostic value of optic nerve sheath diameter and the FOUR score separately, studies that directly address the development of brain death as an outcome and assess these two parameters together in patients followed in the intensive care unit due to severe brain injury are limited [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The combined evaluation of clinical neurological findings and an imaging-based parameter reflecting intracranial pressure elevation may contribute to earlier and more accurate identification of patients at high risk for developing brain death.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to evaluate the role of optic nerve sheath diameter measured at admission and the FOUR score in predicting the development of brain death in patients with severe neurological injury followed in the intensive care unit due to severe brain injury. In addition, we sought to determine the potential contribution of the combined use of these two parameters in discriminating the development of brain death.\u003c/p\u003e"},{"header":"METHODOLOGY","content":"\u003ch3\u003e\u003cstrong\u003eStudy Design and Patient Selection\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis single-center, retrospective study was conducted to evaluate the role of optic nerve sheath diameter (ONSD) and the FOUR score in predicting the development of brain death in patients admitted to the intensive care unit due to diffuse brain injury (hemorrhage, ischemia, hypoxia, etc.). The study was carried out in the Anesthesiology and Reanimation Intensive Care Units of Bursa City Hospital.\u003c/p\u003e\n\u003cp\u003ePatients aged 18 years and older who were admitted to the intensive care unit from the emergency department, had a GCS score of 7 or less,\u0026nbsp;were followed with a diagnosis of severe acute brain injury, were not operated on, and were under mechanical ventilation support were included in the study. Patients younger than 18 years, those with neurological disorders secondary to intoxication, hypercapnia, or sepsis, patients who had undergone decompression surgery, those with maxillofacial trauma or skull base fractures, patients followed in the intensive care unit for less than 24 hours, and patients without cranial computed tomography (CT) evaluation in the emergency department were excluded.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eDemographic characteristics (age, sex), indications for intensive care unit admission, comorbidities, and clinical scores (GCS, FOUR score, and Acute Physiology and Chronic Health Evaluation [APACHE] II score) were retrospectively recorded from patient files and electronic medical records. GCS and FOUR scores were determined based on clinical assessment at the time of intensive care unit admission. The Glasgow Coma Scale (GCS), Full Outline of UnResponsiveness (FOUR) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score applied in this study are previously established and validated clinical scoring systems, and were not developed specifically for this research. The original publications describing these scales have been cited accordingly[9,22,23].\u003c/p\u003e\n\u003cp\u003eIn addition, a modified FOUR score incorporating optic nerve sheath diameter (ONSD) as an additional parameter was developed for exploratory purposes in the present study. This modified score was designed to assess the potential complementary value of ONSD and has not been externally validated. The scoring system is presented in Supplementary Table 1.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eOptic Nerve Sheath Diameter Measurement\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eOptic nerve sheath diameter measurements were performed using cranial computed tomography images obtained at the time of intensive care unit admission. Measurements were made for both eyes, 3 mm posterior to the globe, on transverse sections, and recorded in millimeters [8]. All optic nerve sheath diameter measurements were performed by a single experienced physician in order to minimize measurement variability. Interobserver reliability analysis could not be performed due to the retrospective design of the study.\u003c/p\u003e\n\u003cp\u003eOptic nerve sheath diameter values were additionally categorized and scored in accordance with the literature and used in the analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eModified FOUR Score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the value added by ONSD to the FOUR score, a modified FOUR score has been developed. ONSD has been added as the 5th parameter to the FOUR score. The literature reports that ONSD is up to 4.0 mm in children younger than 1 year, 4.5 mm in those aged 1-18 years, and 5.0 mm in adults [5,6]. In patients followed up for subarachnoid hemorrhage, an ONSD measurement higher than 5.5 mm has been shown to significantly indicate high intracranial pressure [7]. In the study by \u0026Ccedil;evikalp et al., it was determined that an ONSD above 6.62 mm is a cut-off value for predicting brain death. Based on these studies, the scoring system outlined in Table 1 was developed. The modified FOUR score was developed for exploratory purposes and was not intended to replace the original FOUR score or to serve as a validated diagnostic tool.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eOutcome Measure\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe primary outcome of the study was the development of brain death during intensive care unit follow-up. During follow-up, patients were categorized into two groups: those who developed brain death (BD group) and those who did not develop brain death (non-BD group), and clinical, radiological, and score-based variables were compared between the groups.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eBrain Death Determination Process\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eIn T\u0026uuml;rkiye, the framework for brain death determination is defined by national legislation and regulations [1]. According to these regulations, brain death is defined as the permanent and irreversible loss of all functions of the brain, brainstem, and cerebellum. For the diagnosis of brain death, after identifying the structural cause leading to brain injury and excluding reversible conditions, the presence of deep coma, absence of brainstem reflexes, and a positive apnea test must be demonstrated clinically. In addition, confirmation that the state of deep coma persists after the legally mandated observation period is required to establish the diagnosis of brain death. When a confirmatory test assessing cerebral circulation is used for diagnosis, the absence of blood flow in all intracerebral arteries and their branches is required.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of \u003cstrong\u003e316\u0026nbsp;\u003c/strong\u003epatients admitted to the intensive care unit due to severe brain injury\u0026nbsp;were included in the study (Figure 1). The mean age of the cohort was 59.37\u0026plusmn;20.86 years, and \u003cstrong\u003e63.9%\u003c/strong\u003e were male.\u003c/p\u003e\n\u003cp\u003eDuring follow-up, patients were categorized into two groups: those who developed brain death (\u003cstrong\u003eBD group\u003c/strong\u003e) and those who did not (\u003cstrong\u003enon-BD group\u003c/strong\u003e). The non-BD group was significantly older than the BD group (60.44 \u0026plusmn; 21.55 vs 55.86 \u0026plusmn; 18.27 years, p = 0.016). Sex distribution did not differ between groups (p = 0.891). (Table 2).\u003c/p\u003e\n\u003cp\u003eAPACHE II scores were similar between groups (p = 0.086). In contrast, neurological scores were significantly lower in the BD group, with both \u003cstrong\u003eGCS\u003c/strong\u003e and \u003cstrong\u003eFOUR\u003c/strong\u003e scores showing marked differences compared with the non-BD group (p \u0026lt; 0.001 for both). Length of ICU stay was significantly longer in the non-BD group (30.55 \u0026plusmn; 24.66 vs 8.38 \u0026plusmn; 6.20 days, p \u0026lt; 0.001) (Table 2).\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eOptic Nerve Sheath Diameter\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eOptic nerve sheath diameter was significantly higher in the BD group (6.30 \u0026plusmn; 0.50 mm) compared with the non-BD group (4.38 \u0026plusmn; 0.61 mm, p \u0026lt; 0.001). While transverse diameter did not differ between groups (p = 0.194), the optic nerve\u0026ndash;to\u0026ndash;transverse diameter ratio was significantly higher in the BD group (0.28 \u0026plusmn; 0.03 vs 0.20 \u0026plusmn; 0.03, p \u0026lt; 0.001) (Table 3).\u003c/p\u003e\n\u003cp\u003eROC analysis demonstrated excellent discriminative performance of ONSD for predicting brain death, with a cut-off value of \u003cstrong\u003e\u0026gt;5.62 mm\u003c/strong\u003e yielding a sensitivity of \u003cstrong\u003e98.65%\u003c/strong\u003e and a specificity of \u003cstrong\u003e97.52%\u003c/strong\u003e (AUC: \u003cstrong\u003e0.992\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e 95% CI: 0.975\u0026ndash;0.999; p \u0026lt; 0.001) (Figure 2). In contrast, the modified FOUR score showed high sensitivity but limited specificity at a cut-off value of \u003cstrong\u003e\u0026le;9\u003c/strong\u003e (93.24% sensitivity, 34.71% specificity; AUC: \u003cstrong\u003e0.591\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e p = 0.007) (Table 3)( Figure 2).\u003c/p\u003e\n\u003cp\u003eIn multivariable logistic regression analysis, including demographic, clinical, and radiological variables, \u003cstrong\u003eONSD was the only independent predictor\u003c/strong\u003e of brain death development. Each 1-mm increase in ONSD was associated with a \u003cstrong\u003e345.7-fold increase\u003c/strong\u003e in the risk of brain death (OR: 345.7; 95% CI: 36.6\u0026ndash;3266.7; p \u0026lt; 0.001). The model explained \u003cstrong\u003e91.1%\u003c/strong\u003e of outcome variability (Table 4).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study demonstrated significant associations between the development of brain death and both clinical neurological scores and imaging-derived parameters in patients with severe brain injury monitored in the intensive care unit. Patients who progressed to brain death exhibited significantly lower FOUR and GCS scores, alongside significantly higher ONSD and optic nerve\u0026ndash;to\u0026ndash;transverse diameter ratios. Considering the results of ROC and multivariate analyses, ONSD emerged as a strong and independent predictor of brain death. In contrast, the FOUR score showed high sensitivity but limited overall discriminatory ability. Collectively, these findings indicate that integrating clinical neurological assessments with objective imaging markers of elevated intracranial pressure may enhance prognostic accuracy in this critically ill population.\u003c/p\u003e \u003cp\u003e The FOUR score was developed to provide a more comprehensive clinical assessment than the GCS, particularly in mechanically ventilated patients in the intensive care unit, as it incorporates eye response, motor response, brainstem reflexes, and respiratory pattern (9). Previous studies have demonstrated an association between lower FOUR scores and increased mortality, as well as poorer neurological outcomes. In addition, when compared to the GCS, it may offer greater accuracy in predicting short-term mortality in certain intensive care populations [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Nevertheless, the FOUR score remains a functional assessment based on clinical examination and does not incorporate objective measures that directly reflect underlying pathophysiological processes, such as elevated intracranial pressure.\u003c/p\u003e \u003cp\u003eThe optic nerve sheath is susceptible to changes in intracranial pressure because it is anatomically continuous with the subarachnoid space. When intracranial pressure increases, the transmission of cerebrospinal fluid to the optic nerve sheath results in a measurable expansion of its diameter [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Numerous studies have demonstrated that ONSD measurements correlate significantly with invasive intracranial pressure monitoring and are associated with increased mortality and poor neurological outcomes [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, these findings support the role of optic nerve sheath diameter as an objective marker of intracranial hypertension with potential value in prognostic assessment. Although most studies evaluating optic nerve sheath diameter have used ultrasonography, computed tomography\u0026ndash;based measurements offer higher anatomical resolution and are less operator-dependent. In the present study, CT-based ONSD assessment provided a standardized and reproducible approach in a retrospective intensive care cohort.\u003c/p\u003e \u003cp\u003eAlthough the relevant studies in the literature have demonstrated associations between increased ONSD, elevated intracranial pressure, catastrophic brain injury, and poor neurological outcomes, investigations that specifically evaluate brain death as an endpoint remain limited [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Among the few studies addressing this issue, \u0026Ccedil;evikkalp et al. reported an ONSD threshold of 6.62 mm for predicting the development of brain death in patients monitored for intracranial hemorrhage [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the present study, a lower cut-off value (\u0026gt;\u0026thinsp;5.62 mm) showed strong discriminatory performance, with high sensitivity and specificity for predicting brain death. This discrepancy may be attributable to differences in study design and patient populations. Previous research in neuro\u0026ndash;intensive care settings has suggested that ultrasonography-based ONSD measurements can serve as a complementary tool in prognostic assessment [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Similarly, studies using computed tomography have shown that increased ONSD values non-invasively reflect dynamic changes in intracranial pressure and may indicate advanced cerebral injury [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, a recent systematic review and meta-analysis by Xu et al. confirmed that ONSD is a reliable non-invasive marker of intracranial hypertension in traumatic brain injury [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Taken together, these findings support the consideration of ONSD as a valuable prognostic marker in the progression toward brain death in patients with severe brain injury.\u003c/p\u003e \u003cp\u003eIn this study, the observation of significantly lower FOUR scores alongside significantly higher ONSD and optic nerve\u0026ndash;to\u0026ndash;transverse diameter ratios in patients who developed brain death indicates that optic nerve sheath diameter is a critical parameter with prognostic, as well as diagnostic, significance. The identification of ONSD as an independent predictor in multivariate analyses further underscores the central role of elevated intracranial pressure in the pathophysiological process leading to brain death.\u003c/p\u003e \u003cp\u003eROC analysis demonstrated that a modified FOUR score cut-off value of \u0026le;\u0026thinsp;9 yielded high sensitivity (93.24%) but low specificity (34.71%). This pattern suggests that the modified FOUR score functions effectively as a screening tool for identifying patients at risk of developing brain death, while having limited ability to discriminate those who will not progress to this outcome. Given that the FOUR score is a clinically based scale reflecting early and relatively non-specific manifestations of severe neurological injury, its high sensitivity coupled with low specificity is not unexpected. Moreover, in the national clinical context, the diagnosis of brain death is defined by the irreversible loss of all brain functions, including the brain, brainstem, and cerebellum, and is frequently supported by confirmatory tests assessing cerebral circulation. This diagnostic framework may further limit the discriminatory capacity of the FOUR score, as it does not directly assess the complete cessation of global cerebral blood flow. Consequently, some patients with profound clinical neurological impairment and low FOUR scores may not yet fulfill the formal diagnostic criteria for brain death. It should be emphasized that the modified FOUR score proposed in this study has not been externally validated and should be interpreted as an exploratory screening tool rather than a definitive prognostic model.\u003c/p\u003e \u003cp\u003eIn contrast, in the present study, ONSD emerged as a robust objective predictor of brain death, demonstrated by its high discriminatory performance in ROC analysis and its identification as an independent predictor in multivariate analysis. The combined interpretation of these analyses indicates that the modified FOUR score alone lacks sufficient diagnostic accuracy; however, when integrated with an objective, pathophysiologically grounded measure such as ONSD, it may serve as a complementary clinical tool that facilitates the early identification of patients at high risk of progressing to brain death.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Its single-center, observational design limits the generalizability of the findings. The relatively small sample size precluded detailed subgroup analyses, and the assessment of ONSD at a single time point did not allow evaluation of dynamic changes in intracranial pressure over time. Optic nerve sheath diameter was assessed at a single time point using computed tomography, which did not allow evaluation of dynamic intracranial pressure changes or interobserver variability.\u003c/p\u003e \u003cp\u003eAdditionally, brain death was diagnosed using clinical criteria and ancillary tests, and it was not possible to control for all potential confounding factors. The modified FOUR score introduced in this study has not undergone external validation, which limits its generalizability.\u003c/p\u003e \u003cp\u003eIn conclusion, ONSD emerged as a strong and independent predictor of brain death in patients admitted to the intensive care unit due to severe brain injury. The integration of clinical neurological assessments with objective indicators of intracranial pressure may facilitate the early identification of patients at high risk for brain death. To more clearly establish the clinical utility of this combined approach, prospective, multicenter studies with brain death as the primary endpoint are warranted.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGCS: Glasgow Coma Scale\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;FOUR: Full Outline of UnResponsiveness\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ONSD: Optic Nerve Sheath Diameter\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ICU: Intensive Care Unit\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;APACHE II: Acute Physiology and Chronic Health Evaluation II\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis study was approved by the Bursa City Hospital Ethics Committee and conducted in accordance with the Declaration of Helsinki. Due to the retrospective nature of the study, the requirement for informed consent was waived.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the patient or their legal representatives.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eE\u0026Ccedil; conceived and designed the study. G\u0026Ccedil; collected the data. EU performed the statistical analysis. All authors interpreted the data, drafted the manuscript, and approved the final version.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eArsava EM, \u0026Uuml;nal A. Turkish Neurological Society Diagnostic Guidelines for Brain Death*.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Groot YJ, Jansen NE, Bakker J, Kuiper MA, Aerdts S, Maas AIR, et al. Imminent brain death: point of departure for potential heart-beating organ donor recognition. Intensive Care Med. 2010;36(9):1488\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalih F, Holtkamp M, Brandt SA, Hoffmann O, Masuhr F, Schreiber S, et al. Intracranial pressure and cerebral perfusion pressure in patients developing brain death. J Crit Care. 2016;34:1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLe Roux P, Menon DK, Citerio G, Vespa P, Bader MK, Brophy GM et al. Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. Neurocrit Care. 2014;21 Suppl 2(Suppl 2):1\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlaivas M, Theodoro D, Sierzenski PR. Elevated intracranial pressure detected by bedside emergency ultrasonography of the optic nerve sheath. Acad Emerg Med. 2003;10(4):376\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLe A, Hoehn ME, Smith ME, Spentzas T, Schlappy D, Pershad J. Bedside sonographic measurement of optic nerve sheath diameter as a predictor of increased intracranial pressure in children. Ann Emerg Med. 2009;53(6):785\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaiman M, Sigal T, Kimiagar I, Bekerman I. Noninvasive assessment of the intracranial pressure in non-traumatic intracranial hemorrhage. J Clin Neurosci. 2016;34:177\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ccedil;evikkalp E, D\u0026uuml;ndar HZ, Ocakoğlu G. Evaluation of Optic Nerve Sheath Diameter for Prediction of the Development of Brain Death in Patients Admitted to the Intensive Care Unit with Intracranial Hemorrhage. Exp Clin Transpl. 2023;21(3):259\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWijdicks EFM, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol. 2005;58(4):585\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIyer VN, Mandrekar JN, Danielson RD, Zubkov AY, Elmer JL, Wijdicks EFM. Validity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc. 2009;84(8):694\u0026ndash;701.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamazani J, Hosseini M. Prediction of Mortality in the Medical Intensive Care Unit with Serial Full Outline of Unresponsiveness Score in Elderly Patients. Indian J Crit Care Med. 2022;26(1):94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCannata G, Pezzato S, Esposito S, Moscatelli A. Optic Nerve Sheath Diameter Ultrasound: A Non-Invasive Approach to Evaluate Increased Intracranial Pressure in Critically Ill Pediatric Patients. Diagnostics 2022, Vol 12, 2022;12(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen LM, Wang LJ, Hu Y, Jiang XH, Wang YZ, Xing YQ. Ultrasonic measurement of optic nerve sheath diameter: a non-invasive surrogate approach for dynamic, real-time evaluation of intracranial pressure. Br J Ophthalmol. 2018;103(4):437.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhandari D, Udupi Bidkar P, Adinarayanan S, Narmadhalakshmi K, Srinivasan S. Measurement of changes in optic nerve sheath diameter using ultrasound and computed tomography scan before and after the ventriculoperitoneal shunt surgery in patients with hydrocephalus - A prospective observational trial. Br J Neurosurg. 2019;33(2):125\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoldatos T, Karakitsos D, Chatzimichail K, Papathanasiou M, Gouliamos A, Karabinis A. Optic nerve sonography in the diagnostic evaluation of adult brain injury. Crit Care. 2008;12(3):R67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SH, Kim HS, Yun SJ. Optic nerve sheath diameter measurement for predicting raised intracranial pressure in adult patients with severe traumatic brain injury: A meta-analysis. J Crit Care. 2020;56:182\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSekhon MS, Griesdale DE, Robba C, McGlashan N, Needham E, Walland K, et al. Optic nerve sheath diameter on computed tomography is correlated with simultaneously measured intracranial pressure in patients with severe traumatic brain injury. Intensive Care Med. 2014;40(9):1267\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang X, Ma D, Li W, Ma J, Bi K, Qiao Y, et al. Correlation between optic nerve sheath diameter measured by bedside ultrasound and intracranial pressure in neurologically ill patients in a Chinese population. BMC Neurol. 2024;24(1):452.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu J, Song Y, Shah Nayaz BM, Shi W, Zhao Y, Liu Y, et al. Optic Nerve Sheath Diameter Sonography for the Diagnosis of Intracranial Hypertension in Traumatic Brain Injury: A Systematic Review and Meta-Analysis. World Neurosurg. 2024;182:136\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen W, Zhang X, Ye X, Ying P. Diagnostic accuracy of optic nerve sheath diameter on ultrasound for the detection of increased intracranial pressure in patients with traumatic brain injury: A systematic review and meta-analysis. Biomed Rep 2023;19(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMengi T, Ka\u0026ccedil;maz M, Yakar H. Prognostic value of optic nerve sheath diameter in coma. TURKISH J Cerebrovasc Dis. 2022;28(2):80\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOh TE, Hutchinson R, Short S, Buckley T, Lin E, Leung D. Verification of the Acute Physiology and Chronic Health Evaluation scoring system in a Hong Kong intensive care unit. Crit Care Med. 1993;21(5):698\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReith FC, Brennan PM, Maas AI, Teasdale GM. Lack of Standardization in the Use of the Glasgow Coma Scale: Results of International Surveys. J Neurotrauma. 2016;33(1):89\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Scoring system for optic nerve sheath diameter measurements\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eONSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt; 5 mm\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e5-5.5 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e5.5-6.62 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026gt; 6.62 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eNumerical score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparison of demographic, clinical, and radiological characteristics between groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBrain Death\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntracranial hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e26 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e88 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.891\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e48 (64.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e154 (63.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubarachnoid hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e30 (40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e85 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParenchymal hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e19 (25.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e90 (37.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraventricular hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e20 (27.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e43 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIschemia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e17 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypoxia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePons hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e1 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e3 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypertension\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e33 (44.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e97 (40.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.490\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes mellitus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e14 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e68 (28.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.154\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoronary artery disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e14 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e27 (11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.123\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerebrovascular disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e12 (16.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e40 (16.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e1.000\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChronic obstructive pulmonary disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e2 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e13 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.534\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignancy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e2 (2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e28 (11.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.040\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e20 (27.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e119 (49.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e55.86 \u0026plusmn; 18.27\u003c/p\u003e\n \u003cp\u003e57 (4 - 84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e60.44 \u0026plusmn; 21.55\u003c/p\u003e\n \u003cp\u003e66 (0 - 95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOptic nerve sheath diameter (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e6.30 \u0026plusmn; 0.50\u003c/p\u003e\n \u003cp\u003e6.33 (5.38 \u0026ndash; 7.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4.38 \u0026plusmn; 0.61\u003c/p\u003e\n \u003cp\u003e4.35 (3.14 \u0026ndash; 6.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransverse diameter (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e22.32 \u0026plusmn; 1.11\u003c/p\u003e\n \u003cp\u003e22.19 (19.20 \u0026ndash; 25.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e22.48 \u0026plusmn; 0.99\u003c/p\u003e\n \u003cp\u003e22.42 (19.76 \u0026ndash; 25.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.194\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eONSD / Transverse diameter ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.28 \u0026plusmn; 0.03\u003c/p\u003e\n \u003cp\u003e0.28 (0.22 \u0026ndash; 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.20 \u0026plusmn; 0.03\u003c/p\u003e\n \u003cp\u003e0.20 (0.14 \u0026ndash; 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e8.38 \u0026plusmn; 6.20\u003c/p\u003e\n \u003cp\u003e6 (2 - 25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e30.55 \u0026plusmn; 24.66\u003c/p\u003e\n \u003cp\u003e24.5 (2 - 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPACHE score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e19.18 \u0026plusmn; 8.06\u003c/p\u003e\n \u003cp\u003e20.5 (3 - 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e18.31 \u0026plusmn; 8.69\u003c/p\u003e\n \u003cp\u003e18.0 (0 - 47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e0.086\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGCS score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4.54 \u0026plusmn; 1.56\u003c/p\u003e\n \u003cp\u003e4 (3 - 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e5.84 \u0026plusmn; 2.06\u003c/p\u003e\n \u003cp\u003e6 (3 - 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFOUR score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e3.35 \u0026plusmn; 3.17\u003c/p\u003e\n \u003cp\u003e2 (0 \u0026ndash; 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e6.39 \u0026plusmn; 4.12\u003c/p\u003e\n \u003cp\u003e6 (0 \u0026ndash; 16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e Pearson chi-square test; \u003cstrong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e Fisher\u0026ndash;Freeman\u0026ndash;Halton chi-square test; \u003cstrong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e Yates\u0026rsquo; chi-square test; \u003cstrong\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/strong\u003e Fisher\u0026rsquo;s exact test; \u003cstrong\u003e\u003csup\u003ee\u003c/sup\u003e\u003c/strong\u003e Mann\u0026ndash;Whitney U test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eONSD\u003c/strong\u003e, optic nerve sheath diameter; \u003cstrong\u003eGCS\u003c/strong\u003e, Glasgow Coma Scale; \u003cstrong\u003eFOUR\u003c/strong\u003e, Full Outline of UnResponsiveness; \u003cstrong\u003eAPACHE\u003c/strong\u003e, Acute Physiology and Chronic Health Evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. ROC analysis results for predicting brain death\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"702\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCut-off\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYouden Index\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC (%95 CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity (%95 CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity (%95 CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eONSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026gt;5.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.9617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.992 (0.975 \u0026ndash; 0.999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e98.65 (92.7 \u0026ndash; 100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e97.52 (94.7 \u0026ndash; 99.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003emFOUR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026le;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.2795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.591 (0.534 \u0026ndash; 0.645)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e93.24 (84.9 \u0026ndash; 97.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e34.71 (28.7 \u0026ndash; 41.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.007\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eROC Analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eONSD\u003c/strong\u003e, optic nerve sheath diameter; \u003cstrong\u003emFOUR\u003c/strong\u003e, modified Full Outline of UnResponsiveness; \u003cstrong\u003eAUC\u003c/strong\u003e, area under the curve; \u003cstrong\u003eCI\u003c/strong\u003e, confidence interval.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDependent variable:\u003c/strong\u003e Development of brain death\u003cbr\u003e\u003cstrong\u003eIndependent variables:\u003c/strong\u003e Age, GCS, modified FOUR score, transverse diameter, optic nerve sheath diameter\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Multivariate logistic regression analysis for predictors of brain death\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"612\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStandard Error\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWald\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003edf\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExp(B)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%95 CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e-0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e5.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.854 \u0026ndash; 0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eONSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e5.846\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e1.146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e26.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e345.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e36.6 \u0026ndash; 3266.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e-31.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e6.445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e24.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eModel explanatory power:\u003c/strong\u003e 91.1%\u0026nbsp;\u003c/p\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":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Optic nerve sheath diameter, Brain death, FOUR score, Severe brain injury, Neurocritical care","lastPublishedDoi":"10.21203/rs.3.rs-8732205/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8732205/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBrain death is a catastrophic outcome of severe brain injury, most commonly associated with progressive intracranial hypertension. Early identification of patients at risk for brain death remains challenging. Optic nerve sheath diameter (ONSD), reflecting intracranial pressure, and the Full Outline of UnResponsiveness (FOUR) score, assessing neurological function, have been proposed as prognostic tools; however, evidence regarding their combined use is limited.\u003c/p\u003e\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo evaluate the predictive value of ONSD and the FOUR score, individually and in combination, for the development of brain death in patients admitted to the intensive care unit with severe brain injury.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis single-center, retrospective study included adult patients with severe neurological impairment (Glasgow Coma Scale\u0026thinsp;\u0026le;\u0026thinsp;7). ONSD was measured on admission cranial computed tomography scans. Clinical data and neurological scores were recorded. A modified FOUR score incorporating ONSD as a fifth parameter was developed. The primary outcome was the development of brain death during intensive care follow-up.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong 316 patients, those who developed brain death had significantly lower GCS and FOUR scores and significantly higher ONSD values (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). An ONSD cutoff value of \u0026gt;\u0026thinsp;5.62 mm demonstrated excellent discriminative performance for predicting brain death (AUC: 0.992; sensitivity 98.65%, specificity 97.52%). The modified FOUR score showed high sensitivity but limited specificity, suggesting a screening rather than a definitive discriminative role. In multivariable analysis, ONSD was the only independent predictor of brain death (OR: 345.7; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eONSD is a strong and independent predictor of brain death in patients with severe brain injury. While the FOUR score provides valuable clinical information, its prognostic utility appears enhanced when combined with objective markers of intracranial hypertension. The modified FOUR score may serve as a complementary screening tool, whereas ONSD offers robust discriminatory power. Integrating clinical neurological assessment with imaging-based parameters may improve early risk stratification for brain death.\u003c/p\u003e","manuscriptTitle":"Evaluation of the Combined Use of Optic Nerve Sheath Diameter and the FOUR Score in Predicting Brain Death in Patients with Severe Brain Injury Admitted to the Intensive Care Unit","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 16:35:04","doi":"10.21203/rs.3.rs-8732205/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-02T05:44:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323265262924324153320659735473473145521","date":"2026-04-23T16:38:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-17T18:03:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-14T22:40:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T13:20:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-04T12:29:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-02-04T12:13:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"297b1f5e-e666-4f15-bb1a-264564d94d0c","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-02T05:44:55+00:00","index":89,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-22T16:35:04+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 16:35:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8732205","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8732205","identity":"rs-8732205","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}