Emergency (2013); 1 (1): ***-*** This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2013 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 15 Emergency (2013); 1 (1): 15-19 ORIGINAL RESEARCH Sonographic Optic Nerve Sheath Diameter as a Screening Tool for Detection of Elevated Intracranial Pressure Afshin Amini1, Razieh Eghtesadi1*, Ali Mohammad Feizi2, Behnam Mansouri3, Hamid Kariman1, Ali Arhami Dolatabadi1, Hamidreza Hatamabadi1, Ali Kabir1 1. Department of Emergency Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Department of Radiology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3. Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abstract Introduction: Timely diagnosis and treatment of post-traumatic elevated intracranial pressure (EICP) could be reduced morbidity and mortality, and improved patients’ outcome. This study is trying to evaluate the diagnostic accuracy of sonographic optic nerve sheath diameter (ONSD) in detection of EICP. Methods: Sonographic ONSD of patients with head trauma or cerebrovascular accident suspicious for EICP were evaluated by a trained chief resident of emergency medicine, who was blind to the clinical and brain computed tomography scan (BCT) find- ings of patients. Immediately after ultrasonography, BCT was performed and reported by an expert radiologist without awareness from other results of the patients. Finally, ultrasonographic and BCT findings regarding EICP were compared. To evaluate the ability of sonographic ONSD in predicting the BCT findings and obtain best cut- off level, receiver operating characteristic (ROC) curve were used. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of so- nographic ONSD in determining of EICP was calculated. P < 0.05 was considered as statistically significant. Re- sults: There were 222 patients (65.3% male), with mean age of 42.2±19.5 years (range: 16-90 years). BCT showed signs of EICP, in 28 cases (12.6%). The means of the ONSD in the patients with EICP and normal ICP were 5.5 ± 0.56 and 3.93 ± 0.53 mm, respectively (P<0.0001). ROC curve demonstrated that the best cut off was 4.85 mm. Sensitivity, specificity, PPV, NPV, PLR, and NLR of ONSD for prediction of EICP were 96.4%, 95.3%, 72.2%, 98.9%, 20.6, and 0.04, respectively. Conclusion: Sonographic diameter of optic nerve sheath could be considered as an available, accurate, and noninvasive screening tool in determining the elevated intracranial pressure in ca s- es with head trauma or cerebrovascular accident. Key words: Intracranial pressure; traumatic brain injury; ultrasonography; optic nerve; tomography Cite this article as: Amini A, Eghtesadi R, Feizi AM, Mansouri B, Kariman H, Arhami Dolatabadi A, Hatamabadi H, Kabir A. Sonographic optic nerve sheath diameter as a screening tool for detection of elevated intracranial pressure. Emergency. 2013; 1(1):15-9. Introduction:1 ead injury is the most common cause of road- traffic-related morbidity and mortality of all ages (1). Traumatic brain injuries and related increasing intracranial pressure (EICP) might result in the worsening of patient outcomes (2). Timely diagno- sis and treatment of post-traumatic EICP could be re- duced morbidity and mortality of patients. There are some invasive, expensive or expert needed methods as lumbar puncture, magnetic resonance imaging (MRI), and computed tomography scan (CT-scan) for detection of EICP (3). Physical examination is not always reliable and also, some signs of EICP such as pupil edema are late coming or hardly detected (4). So, reliable, accessi- *Corresponding Author: Razieh Eghtesadi; Department of Emer- gency Medicine, Imam Hossein Hospital, Shahid Madani Avenue, Teh- ran, Iran. Tel: +989136470851; Fax:+983117923445; Email: razieeqtesadi@yahoo.com Received: 1 October 2013; Accepted: 19 November 2013 ble, easy to learn and noninvasive technique for this purpose, like Sonography, is of interest for clinician. Some studies have assessed the diagnostic accuracy of sonography in animal models, children, and adults in emergent or even in healthy subjects (5-9). These stud- ies were heterogenous from different target population in different settings and their results are not completely applicable for other persons. Our previous study, showed that the sonographic ONSD might be consid- ered as a strong and accurate predicting factor for de- tection of EICP (10). In this study, we prospectively evaluated the diagnostic accuracy of sonography for detecting EICP in a setting of emergency patients with head trauma or suspicious cerebrovascular accident in a relatively larger sample than previous similar studies. Moreover, we intended to determine the best cut off values of ONSD for detecting EICP in comparison with brain computed tomography scan (BCT) findings. H This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2013 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 16 Amini et al Methods: Study design and setting In this diagnostic trial, we recruited 222 patients suspi- cious for EICP due to head trauma or cerebrovascular accident referring to emergency department of Imam Hossien Hospital, Tehran, Iran between May and Octo- ber 2011. The protocol of this study was reviewed and approved by Shahid Beheshti University of Medical Sci- ences Ethics Committee (code: 6476). The study proto- col conformed to the ethical guidelines of the Declara- tion of Helsinki. After complete explanation about the procedure for the patient, written informed consent was received. Surrogate consent by guardian was ob- tained in case patients with altered mental status. Participants The subjects with head trauma or cerebrovascular acci- dent were enrolled. Cases with age < 16, direct trauma to the eye, ophthalmic diseases, and under treatment with medications affecting on intracranial pressure were excluded. Sample size was determined according to sample size calculation for formula of diagnostic tests, considering sensitivity=0.8, specificity=0.8, and α=0.05. Therefore, sample size was estimated to be 222 cases. Intervention Before doing brain CT-scan for definite diagnosis, ONSD of both eyes was determined by ultrasonography. We did ultrasonography before awareness from the result of BCT to prevent diagnostic suspicious bias. Sonog- rapher was also blind to the patient’s clinical condition. Ultrasongraphies of the optic nerve was performed by chief resident of emergency medicine who was trained for measurement of ONSD by a radiologist. Trans- orbital ultrasonography of the optic nerve was per- formed using a 7.5 MHz linear transducer (HS2000, Honda, Korea) sized 5.5×1 cm. The patient was relaxed, calm, in supine position with closed eyes. It was done from the most upper part of the upper eyelid, 3 mm before entrance of the optic nerve to the globe. The ONSD was calculated as the horizontal distance be- tween the 2 cursors (Figure 1). One time measurement was taken for each optic nerve. The mean ONSD regis- tered was the average value obtained from measure- ments of both right and left eyes, despite the fact that previous studies have shown the presence of intra- ocular symmetry between the OND/ONSDs of fellow eyes (11, 12). Immediately after ultrasonography, BCT was performed and reported by one expert radiologist without awareness from the results of the sonography. Signs of EICP in BCT were effacement of sulci, signifi- cant edema, midline shifting, and collapse of ventri- cle(s). Finally, results of ultrasonography were com- pared with BCT findings. Age, gender, level of consciousness according to Glas- gow Coma Scale (GCS), type of injury (trauma or cere- brovascular accident), ONSD of both eyes by ultraso- nography and BCT findings were determined in all pa- tients. Statistical analysis We used mean and standard deviation, for description of quantitative variables. The relation of GCS and ONSD was assessed using person correlation coefficient. To evaluate the ability of ONSD in predicting the BCT re- sults and obtain best cut-off level, receiver operating characteristic (ROC) curve and its area under the curve (AUC) were used. In addition, in specific cut-point we determined operating characteristics consist of sensi- tivity, specificity, positive predictive value (PPV), nega- tive predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Differences or correlations with P < 0.05 were considered statisti- cally significant. We used STATA version 11.0 statistical software in analysis. Results: There were 222 patients (65.3% male), with mean age of 42.2±19.5 years (range: 16-90 years). A summary of patients’ demographic data is presented in table 1. Type of injury was trauma in 204 cases (91.9%) and cerebro- vascular accident in 18 (8.1%). Only 27 (12.2%) cases had GCS<15. BCT finding was confirmed 28 (12.6%) cases of EICP. Among cases with decreased GCS, 13 (48.1%) patients had positive BCT findings. The means of sonographic ONSD on the left and right sides were 4.2±0.8 and 4.1±0.8 mm, respectively (P = 0.41). The mean of the sonographic diameters of the optic nerve sheath of the two eyes was 4.1 ± 0.8 mm, with no signif- icant relationships with patient age (p=0.99) and gen- der (P=0.19). The means of the ONSD in the patients with EICP and normal ICP were 5.5 ± 0.56 and 3.93 ± 0.53 mm, respectively (P<0.0001). GCS was inversely associated with right (r=-0.37, P<0.001), left (r=-0.26, P<0.001) and mean ONSD (r=-0.33, P<0.001). Roc anal- ysis demonstrated that the best cut off was 4.85 mm (figure 2). Area under the curve for diagnosis of the EICP was 0.95 (95% CI: 0.89-1.0). Sensitivity and speci- ficity of ONSD for prediction of EICP were 96.4 % (95% CI: 83.9-99.8) and 95.3% (95% CI: 90.4-99.9), respec- tively. In addition positive and negative predictive value were 72.2% (95% CI: 67.4-79.2) and 98.9% (95% CI: 95.8-99.8), respectively. Positive and negative like- Figure 1: Sonographic optic nerve sheath diameter (ONSD). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2013 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 17 Emergency (2013); 1 (1): 15-19 lihood ratio of ONSD for detection of EICP was 20.6 (95% CI: 18.2-22.4) and 0.04 (95% CI: 0.02-0.06), re- spectively. Discussion: Based on the main result of this study ONSD had ac- ceptable sensitivity, specificity, NPV, and PPV for detec- tion of EICP at cut-off value of 4.85 mm. The probability to have EICP if ONSD is less than 4.85 mm is 0.04, which is sufficiently very low. Previous studies have consid- ered a cut off range of ONSD in predicting of EICP be- tween 5 and 5.9 mm (table 2). Low PPV in this study, despite high sensitivity and specificity, could be due to low number of cases with positive BCT findings. During last decades, many studies have shown that the ONSD can noninvasively predict the EICP (13-15). One study has been shown that increase of ONSD in cases with EICP occurs faster than other ophthalmoscopic findings (16). However, technique, accuracy, and cut off for detecting EICP are different between these studies. Girisgin et al. have been shown that mean OND in pa- tients suspected to have EICP is significantly higher than the healthy subjects (17). A similar study on 156 Iranian children showed that cases with EICP had sig- nificantly larger mean ONDs (7). We have summarized the results of similar studies in emergency setting or ICU in table 2. It seems it is time to determine the best cut off point for detection of EICP in different subgroups of children, adults, cases with different underlying diseases (trau- ma, cerebrovascular accident and so on), gender, age, and any other important factors which affect the nor- mal or pathologic value of OND and ONSD. As other studies have shown, optic nerve sonography has technical limitations and requires a high level of expertise (18). Sonography may be impossible to per- form because of superficial surgical wounds or severe anatomic alterations in patients with head trauma. Moreover, we should consider that BCT signs are not always correspond to real elevation of the intracranial pressure. Conclusion: Sonographic diameter of optic nerve sheath could be considered as an available, accurate, and noninvasive screening tool in determining the elevated intracranial pressure in cases with head trauma or cerebrovascular accident. Acknowledgment: We would like to express our special thanks from all cases participated in this study. Conflict of interest: There was no conflict of interest. Author’s contribution: All authors contribute in drafting/revising the manu- script, study concept or design, analysis or interpreta- tion of data. References: 1. Montazeri A. Road-traffic-related mortality in Iran: a de- scriptive study. Public Health. 2004;118(2):110-3. 2. Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. The Lancet Neurology. 2007;6(3):215-22. 3. Sankhyan N, Vykunta Raju KN, Sharma S, Gulati S. Manage- ment of raised intracranial pressure. Indian J Pediatr. 2010;77(12):1409–16. 4. Tuite GF, Chong WK, Evanson J, et al. The effectiveness of papilledema as an indicator of raised intracrani al pressure in children with craniosynostosis. Neurosurgery. 1996;38(2): 272-8. Table 1: Basic characteristics of patients Characteristics Total BCT findings P value Negative Positive Age (year) 42.2±19.5 41.9±19.1 44.6±21.8 0.5 GCS 14.8±0.69 14.9±0.37 13.96±1.45 <0.001 Left ONSD (mm) 4.14±0.77 3.65±0.58 5.5±0.52 <0.001 Right ONSD (mm) 4.12±0.76 3.9±0.52 5.5±0.7 <0.001 Mean ONSD (mm) 4.13±0.75 3.9±0.53 5.5±0.56 <0.001 BCT: Brain computer tomography; GCS: Glasgow coma scale; ONSD: Optic nerve sheath diameter Figure 2: Receiver operator characteristic (ROC) curve at various cut offs of optic nerve sheath diameter. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2013 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 18 Amini et al Table 2: Summary of similar studies Study Sample (n) Study population Cut off, gold standard Sensitivity Specificity Le et al. USA 2009 (6) 68 Cases with suspected or con- firmed increased ICP, present- ing to the ED or ICU of an ur- ban, academic, freestanding, tertiary-level children’s hospi- tal, age range: 0-18 years ONSD > 4 mm in infants under 1 year ONSD > 4.5 mm in children > 1 year CT-scan / ventriculostomy / lumbar puncture 96% 48% Kimberly et al. USA 2008 (19) 15 Adult patients in both the ED and the neurologic ICU who had invasive intracranial moni- tors placed as part of their clin- ical care, age > 18 years old ONSD > 5 mm Invasive intracranial moni- tors 88% 93% Karakitsos et al. Greece 2006 (8) 54 Patients with brain injury (GCS < 8), mean age ± SD = 40 ±18.6 OND > 5.9 mm CT-scan 74% 65% Blaivas et al. USA 2003 (20) 14 ED patients with a suspicion of EICP due to possible focal in- tracranial pathology, age > 18 years old ONSD > 5 mm CT-scan 100% 95% Bäuerle et al. Germany 2011 (21) 10 Patients with idiopathic intra- cranial hypertension, age ≥18 years old ONSD > 5.8 mm Measuring the CSF opening pressure by lumbar punc- ture 90% 84% Geeraerts et al. France 2008 (22) 37 Adult patients requiring seda- tion and ICP monitoring after severe traumatic brain injury, subarachnoid hemorrhage, intracranial hematoma, or stroke, age range: 18–76 years ONSD > 5.86 mm Invasive measurement ICP via a parenchymal device 95% 79% Geeraerts et al. UK 2008 (23) 38 Patients requiring ICP monitor- ing after severe traumatic brain injury, mean age ± SD = 35 ± 14 ONSD > 5.82 mm CT-scan 90% 92% Tayal et al. USA 2007 (24) 59 Adult ED patients with sus- pected intracranial injury with possible elevated intracranial pressure without obvious ocu- lar trauma, > 18 years old OND > 5 mm CT-scan 100% 63% Soldatos et al. Greece 2008 (18) 76 Critical care patients, age > 18 years old ONSD > 5.7 mm Invasive ICP measurement using an intraparenchymal catheter 74% 100% Major et al. UK 2011 (25) 26 Adult patients who required CT from the ED, age > 18 years old ONSD > 5 mm CT-scan 86% 100% ED: Emergency department, CT: Computed tomography, GCS: Glasgow coma scale, ICP: Intracranial pressure, ICU: Intensive care unit, OND: Optic nerve diameter, ONSD: Optic nerve sheath diameter, mm: Millimeter; SD: Standard deviation This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Copyright © 2013 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 19 Emergency (2013); 1 (1): 15-19 5. Hamilton DR, Sargsyan AE, Melton SL, et al. Sonography for determining the optic nerve sheath diameter with increasing intracranial pressure in a porcine model. J Ultrasound Med. 2011;30(5):651-9. 6. Le 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):785-91. 7. Akhavan Malayeri A, Bavarian S, Mehdizadeh M. Sonograph- ic evaluation of optic nerve diameter in children with raised intracranial pressure. J Ultrasound Med. 2005;24(2):143–7. 8. Karakitsos D, Soldatos T, Gouliamos A, et al. Transorbital Sonographic Monitoring of Optic Nerve Diameter in Patients With Severe Brain Injury. Transplant Proc. 2006;38(10):3700- 6. 9. Lagrèze WA, Lazzaro A, Weigel M, Hansen HC, Hennig J, Bley TA. Morphometry of the retrobulbar human optic nerve: com- parison between conventional sonography and ultrafast mag- netic resonance sequences. Invest Ophthalmol Vis Sci. 2007; 48(5):1913-7. 10. Amini A, Kariman H, Arhami Dolatabadi A, et al. Use of the sonographic diameter of optic nerve sheath to estimate intra- cranial pressure. The American Journal of Emergency Medi- cine. 2012;31(1):236–9. 11. Ballantyne SA, O'Neill G, Hamilton R, Hollman AS. Observ- er variation in the sonographic measurement of optic nerve sheath diameter in normal adults. Eur J Ultrasound. 2002;15 (3):145-9. 12. Karim S, Clark RA, Poukens V, Demer JL. Demonstration of systematic variation in human intraorbital optic nerve size by quantitative magnetic resonance imaging and histology. In- vest Ophthalmol Vis Sci. 2004;45(4):1047-51. 13. Hansen HC, Helmke K. Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests. J Neurosurg. 1997; 87:34–40. 14. Hansen HC, Helmke K. The subarachnoid space surround- ing the optic nerves. An ultrasound study of the optic nerve sheath. Surg Radiol Anat. 1996;18:323–8. 15. Skalka HW. Neural and dural optic nerve measurements with A-scan ultrasonography. South Med J. 1978;71:399–400. 16. Gangemi M, Cennamo G, Maiuri F, D'Andrea F. Echographic measurement of the optic nerve in patients with intracranial hypertension. Neurochirurgia (Stuttg). 1987;30(2):53-5. 17. Girisgin AS, Kalkan E, Kocak S, Cander B, Gul M, Semiz M. The role of optic nerve ultrasonography in the diagnosis of elevated intracranial pressure. Emerg Med J. 2007;24(4):251- 4. 18. Soldatos 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. 19. Kimberly HH, Shah S, Marill K, Noble V. Correlation of op- tic nerve sheath diameter with direct measurement of intra- cranial pressure. Acad Emerg Med. 2008;15(2):201-4. 20. Blaivas M, Theodoro D, Sierzenski PR. Elevated intracrani- al pressure detected by bedside emergency ultrasonography of the optic nerve sheath. Acad Emerg Med. 2003;10(4):376- 81. 21. Bäuerle J, Nedelmann M. Sonographic assessment of the optic nerve sheath in idiopathic intracranial hypertension. J Neurol. 2011;258(11):2014-9. 22. Geeraerts T, Merceron S, Benhamou D, Vigué B, Duranteau J. Non-invasive assessment of intracranial pressure using ocu- lar sonography in neurocritical care patients. Intensive Care Med. 2008;34(11):2062-7. 23. Geeraerts T, Newcombe VF, Coles JP, et al. Use of T2- weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. Crit Care. 2008;12(5):R114. 24. Tayal VS, Neulander M, Norton HJ, Foster T, Saunders T, Blaivas M. Emergency department sonographic measurement of optic nerve sheath diameter to detect findings of increased intracranial pressure in adult head injury patients. Ann Emerg Med. 2007;49(4):508-14. 25. Major R, Girling S, Boyle A. Ultrasound measurement of optic nerve sheath diameter in patients with a clinical suspi- cion of raised intracranial pressure. Emerg Med J. 2011;28 (8):679-81.