a b s t r a c t

Background: ONSD (optic nerve sheath diameter) is a method used for indirect measurement of the increased in- tracranial pressure. In previous studies, the relation between the increased intracranial pressure and ONSD was analyzed in the patients suffering from cerebrovascular diseases (CVD). In our study, the patients suffering from ischemic CVD were categorized into 4 subgroups according to Oxfordshire Community Stroke Project classifica- tion (OCSP); the relationship between each group and ONSD, and the influence on each eye were analyzed.

Methods: The study included the patients over the age of 18 applying to the emergency department of Malatya State Hospital with the symptoms of stroke between the dates of 1/1/2015 and 1/9/2016. The patients diagnosed with stroke by means of clinical and neuroradiological imaging were examined in 4 subgroups according to Ox- fordshire Community Stroke Project. The aim of the study is to predict the intracranial pressure levels of the patients through ONSD measurement and CT images.

Results: In the comparison of the right and left optic nerve sheath diameters of CVD group and control group, the obtained results were found to be statistically significant (p b 0.001). When the CVD subgroups were compared with the control group in terms of right and left optic nerve sheath diameters, the highest right-left optic nerve sheath diameter was detected to be in TACI (Total Anterior Circulation Infarction) group (p b 0.001).

Discussion/conclusion: In the early cases of CVD, mortality and morbidity can be decreased through the early di- agnosis of the possible existence of ICP increase according to ONSD level.

(C) 2017

1. Background

ONSD is a method used for the indirect measurement of the increase in intracranial pressure [1]. Optic nerve is a part of central nervous sys- tem, and it is covered with dural sheath. Moreover, optic nerve sheath is directly related to the intracranial subarachnoid space. ONSD enlarges in the cases in which ICP shows an increase [2,3]. These changes in ONSD measures can be detected by means of invasive and noninvasive methods. The use of an intracranial device is the gold standard method for the diagnosis of the increase in ICP; however, the use of this method can be difficult because it is an invasive procedure [4]. The disadvan- tages of this method can be considered as the need for a neurosurgeon for the implementation of the invasive procedure, the contradictions such as coagulopathy and thrombocytopenia, and the complications such as malfunction, hemorrhage and infection [5]. CT, MRI and

* Corresponding author.

E-mail address: [email protected] (E. Gokcen).

Transoculer USG can be listed as noninvasive methods in the diagnosis of ICP increase [1,6,7]. Stroke is the third main reason for death in the world, and it preserves its position as a significant cause of morbidity [8]. Dramatic increase in the intracranial pressure has been associated with the deaths of the patients having broad ischemic stroke [9].

This increase in ICP has been generally attributed to the increase of the volume of cerebral edema. However, insufficient information has been recorded about the ICP increase in the patients suffering from mini-stroke and minimal cerebral edema. The main reason of this lack of information is predicted to be the nonuse of the invasive methods of ICP monitorization in this patient group [10].

The measurement of the ICP level after stroke and the determination of the mechanisms causing this condition are quite significant for the developing treatment strategies of stroke. In this study, we divided the patients with ischemic stroke applying to our emergency depart- ment into different groups in accordance with a clinic-based classifica- tion (Oxfordshire Community Stroke Project classification) [11], and we aimed to predict the ICP levels of the patients through ONSD mea- surement and CT images.

http://dx.doi.org/10.1016/j.ajem.2017.04.073

0735-6757/(C) 2017

Table 1

Comparison between the study group and the control group.

	CVD	Control	p
AGE	72.4 +- 11.3	72.6 +- 9.7	NS
R-ONSD (mm)	5.6(5.1-7.1)	4.9(4.1-6.1)	b0.001
L-ONSD (mm)	5.6(5.0-7.3)	4.9(4.0-6.2)	b0.001

CVD: cerebrovascular disease, R-ONSD: Right optic nerve sheath diameter, L-ONSD: Left optic nerve sheath diameter.

1. Methods

In this study, the patients diagnosed with CVD in the emergency de- partment of Malatya State Hospital between the dates of 1/1/2015 and 1/9/2016 were retrospectively analyzed. (n = 79) of (n = 178) patients diagnosed with CVD were excluded from the study in accordance with the exclusion criteria. (n = 92) control groups were included in the study, and (n = 184) optic nerve diameters were analyzed. The patients diagnosed with stroke by means of clinical and neuroradiological imag- ing were examined in 4 subgroups according to Oxfordshire Communi- ty Stroke Project classification. The patients were classified as having total anterior circulation infarct (TACI), partial anterior circulation in- farct (PACI), posterior circulation infarct (POCI), or lacunar infarct (LACI) based on their maximum neurological defects.

(n = 14) out of (n = 99) patients diagnosed with CVD and included in the study consisted of TACI patients; (n = 30) were PACI patients, and (n = 24) were LACI patients. Both left and right optic nerve sheath diameters of the patients having acute CVD and the control groups were measured separately, and the results were compared to each other. The patients having acute CVD were examined in 4 subgroups according to Oxfordshire Community Stroke Project classification. The right and left optic nerve sheath diameters of the patients in the above-mentioned 4 groups were separately calculated, and the groups were compared to each other in terms of optic nerve sheath diameters. It was aimed to de- termine the side of the optic nerve sheath diameter showing increase and the groups of CVD patients influenced by this increase.

Exclusion criteria

This study excluded the patients under the age of 18 applying to our hospital with the diagnosis of acute CVD, the patients recovering from CVD, the patients having intracranial space occupying lesions, the pa- tients diagnosed with transient ischemic attack, the patients having hemorrhaging stroke, the patients with any kind of ophthalmologic dis- eases influencing the optic nerve diameters, the patients having rheu- matic and vasculitis syndromes, the patients under a medical treatment influencing the cerebrospinal fluid pressure and pregnant patients.

Statistical analysis

Statistical analysis was performed using the Statistics Package for Social Sciences software (ver. 15.0, SPSS Inc., Chicago, IL). The distribu- tion of data was calculated using the normality test. The independent sample t-test was used to compare continuous variables with normal distributions and the Mann-Whitney U test was used to compare vari- ables with non-normal distributions. In the comparison of more than

two groups was used the Kruskal Wallis test for nonparametric data. Re- ceiver operating characteristic (ROC) analysis was used to calculate cut- off values. A value of p b 0.05 was accepted as statistically significant.

1. Results

99 out of 191 patients included in the study were in the study group and they were diagnosed with CVD while 92 patients were included in the control group. 14 patients in CVD group were suffering from TACI; 30 patients had PACI; 31 patients had POCI, and 24 patients were suffer- ing from LACI.

Comparison of the groups

In the comparison of the study group and the control group, right and left optic nerve sheath diameters and systolic and diastolic blood pressures were found to be statistically significant in CVD group (p b 0.001). The comparison between the study group and the control group was summarized in Table 1.

When the CVD subgroups were compared with the control group in terms of right and left optic nerve sheath diameters, statistically signif- icant difference was found between all CVD subgroups and the control group (p b 0.001) (Table 2).

When the CVD subgroups were compared with the control group in terms of right and left optic nerve sheath diameters, the highest right- left optic nerve diameter was found to be in TACI group and the lowest right-left optic nerve sheath diameter was found to be in LACI group (p b 0.001) (Table 2), (Figs. 1, 2).

ROC analysis

Right optic nerve sheath diameter lead to a significant prediction of CVD (AUC = 0.941, p b 0.001). Optimal cut off value was calculated as

5.4 mm with 75% sensitivity and 91% specificity (Fig. 3).

Left optic nerve sheath diameter lead to a significant prediction of CVD (AUC = 0.922, p b 0.001). Optimal cut off value was calculated as

5.3 mm with 80% sensitivity and 84% specificity (Fig. 3).

1. Discussion

This study was performed in order to determine the causes of ONSD differences in the subgroups of the patients suffering from stroke by di- viding the patients having ischemic stroke into 4 subgroups in accor- dance with Oxfordshire Community Stroke Project classification.

In TACI cases that develop as a result of proximal middle cerebral ar-

tery occlusion, usually massive cerebral infarction is observed. The oc- clusion of the Middle cerebral artery is also seen in PACI cases; however, the magnitude of the lesion is lower than the one in TACI cases since the occlusion occurs in distal location or large collateral cir- culation is provided. On the other hand, the disease develops in POCI cases frequently as a result of cerebellum, occipital lob infarcts or occlu- sion of vertebra-Basilar artery. LACI cases include small lacunar infarcts in Basal ganglions or pons [12].

In a study carried out by Yang Y. et al. on 1115 patients having CVD, it was reported that 17.67% of the cases had TACI, that 62.78% had PACI, that 13.72% had POCI, and that 5.83% had lacunar infarct [12]. In another study performed by Sung SF et al., TACI was reported to be 29.6%, POCI

Table 2

Comparison of CVD subgroups with control groups in terms of optic nerve sheath diameter.

	TACI	PACI	POCI	LACI	CONTROL	p
R-ONSD (mm)	6.3(5.2-7.1)	5.7(5.1-6.7)	5.5(5.3-6.4)	5.3(5.1-9.9)	4.9(4.1-6.1)	p b 0.001
L-ONSD (mm)	6.2(5.1-7.3)	5.7(5.4-6.5)	5.7(5.1-6.7)	5.2(5.0-5.8)	4.9(4.0-6.2)	p b 0.001

R-ONSD: Right optic nerve sheath diameter, L-ONSD: Left optic nerve sheath diameter, TACI: total anterior circulation infarct, PACI: partial anterior circulation infarct, POCI: posterior cir- culation infarct, LACI: lacunar infarct.

Fig. 1. Right optic nerve sheath diameters of the study group and the control group.

8.8%, LACI 20.3%, and uncategorized group 3.6% [13]. In our study, on the other hand, TACI was calculated to be 14.14%, PACI 30.30%, POCI 31.31%, and LACI 24.24%.

Optic nerve sheath is an anatomic structure extending through in- tracranial region. Since optic nerve sheath is surrounded with cerebro- spinal fluid, the increase in intracranial pressure leads to the enlargement of optic nerve sheath and especially retrobulbar segment [14]. Intracranial pressure is measured by means of certain invasive methods such as lumbar puncture or ventriculostomy. Ventricular cath- eterization is the gold standard method for the measurement of

intracranial pressure. However, the invasive structure of the method, the need for a neurosurgeon for the implementation of the invasive pro- cedure, technical difficulties, the contradictions such as coagulopathy and thrombocytopenia, and the complications such as hemorrhage and infection are the limiting factors of this method [5].

Kimberley et al. reported in their study that there was a direct rela- tionship between ONSD and ICP [15]. Safak et al., on the other hand, stated that ICP can be measured through noninvasive procedures by de- termining the optic nerve sheath diameters [16]. Dramatic increases in ICP have mostly resulted in deaths of the patients suffering from

Fig. 2. Left optic nerve sheath diameters of the study group and the control group.

Fig. 3. Prediction value of right and left optic nerve sheath diameters for CVD.

broad ischemic stroke [9]. This increase in ICP was always attributed to the enlargement of cerebral edema. This is because ICP measurement studies were invariably carried out on the patients suffering from stroke causing large mass impact [17,18,19].

Sufficient information could not be obtained in the patients having mini-strokes or medium sized strokes, because of the invasiveness of available methods for ICP monitoring in patients [2]. In our study, ONSD increase was found to be statistically significant for both right and left optic nerves in all CVD subgroups (p b 0.001).This result is the indirect indication of significant ICP increase in all CVD subgroups.

The correlation between ONSD and the measurements of noninva- sive computed tomography (CT), ultrasonography (USG) and magnetic resonance imaging (MRI) was previously indicated in the literature [2]. The measurement of optic nerve sheath diameter by means of USG is one of the methods showing the ICP increase indirectly. However, the implementation of USG procedure by an experienced physician is one of the most important factors influencing the achievement of correct re- sults [2]. CT has become a more useful method for the diagnosis of CVD since MRI tests are both expensive and rarely found [2].

Young AM et al. calculated the right eye ONSD as 5.6 +- 2.5 mm and the left eye ONDS as 5.9 +- 3.2 mm in their study [20]. It was reported in another study that there was a significant relationship between ONSD diameter and ICP. Moreover, in the same study, right eye ONSD was found to be 6.7 +- 1.0 mm, and left eye ONSD was found to be 6.7 +-

0.9 mm [21]. In a study carried out by Bekerman et al., it was reported that ONSD increase was observed in 94.3% of the cases in which ICP in- crease developed, and that the former increase was found to be statisti- cally significant. Again, in the same study, right eye ONSD was calculated as 6.2 +- 1.2 mm, and left eye ONSD was calculated as 6.3 +-

0.9 mm [22].

Vaiman et al. reported that the relationship between ICP increase and ONSD was found to be statistically significant in their study carried out 312 adult patients having ICP increase due to head trauma. In the same study, right eye ONSD was calculated as 6.5 +- 1.5 mm, and left eye ONSD was calculated as 6.4 +- 1.3 mm [23]. In our study, on the other hand, right ONSD and left ONSD were found to be 4.9 mm (4.1- 6.1) and 4.9 mm (4-6.2) respectively in the control group while right ONSD and left ONSD were calculated as 5.6 mm (5.1-7.1) and 5.6 mm

(5-7.3) respectively in the patients having CVD and ICP increase. In the comparison of the study group with the control group, right and left optic nerve sheath diameters and ICP increase were detected to be statistically significant in the CVD group (p b 0.001). The relationship between ICP increase and ONSD was analyzed in the CVD subgroups and the control group, and it was found to be significant (p b 0.001). When the CVD subgroups and the control group were compared to each other in terms of right and left optic nerve diameters, the highest right-left optic nerve diameter was found to be in TACI group and the lowest right-left optic nerve sheath diameter was found to be in LACI group (p b 0.001) (Table 2), (Figs. 1, 2). This outcome is also an indirect indicator demonstrating that the highest ICP increase was observed in TACI group, and the lowest ICP increase in LACI group.

Moreover, right ONSD lead to a significant prediction of CVD in our study (AUC = 0.941, p b 0.001). Optimal cut off value was calculated as 5.4 mm with 75% sensitivity and 91% specificity. Left optic nerve sheath diameter lead to a significant prediction of CVD (AUC = 0.922, p b 0.001). Optimal cut off value was calculated as 5.3 mm with 80% sen- sitivity and 84% specificity.

1. Conclusion

It is not always convenient to use invasive methods for the determi- nation of ICP increase in the cases with CVD. ONSD measurement which is a noninvasive procedure is a cost-effective method for observing ICP increase. Our study is the first research in the literature which demon- strates the ICP increase by measuring ONSD in CVD subgroups. We be- lieve that it will make contribution to the further treatment strategies related to ICP in CVD subgroups.

Conflict of interest

None.

Acknowledgement

We are grateful to Res. Asst. Tugce Elif Tasdan for her contribution to English translation of the paper.

References

1. Kalantari H, Jaiswal R, Bruck I, Matari H, Ghobadi F, Weedon J, et al. Correlation of optic nerve sheath diameter measurements by computed tomography and magnetic resonance imaging. Am J Emerg Med 2013;31(11):1595-7.
2. Hassen GW, Bruck I, Donahue J, Mason B, Sweeney B, Saab W, et al. Accuracy of optic nerve sheath diameter measurement by emergency physicians using bedside ultra- sound. J Emerg Med 2015;48(4):450-7.
3. Sekhon 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. Inten- sive Care Med 2014;40(9):1267-74.
4. Dubourg J, Messerer M, Karakitsos D, Rajajee V, Antonsen E, Javouhey E, et al. Indi- vidual patient data systematic review and meta-analysis of optic nerve sheath diam- eter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group. Syst Rev 2013;2:62.
5. Rickert K, Sinson G. Intracranial pressure monitoring. Oper Tech Gen Surg 2003;5: 170-5.
6. Raboel PH, Bartek Jr J, Andresen M, Bellander BM, Romner B. Intracranial pressure monitoring: invasive versus Non-invasive methods-a review. Crit Care Res Prac 2012;2012:950393.
7. Shevlin C. Optic nerve sheath ultrasound for the bedside diagnosis of intracranial hy- pertension: pitfalls and potential. Crit Care Horiz 2015;1:22-30.
8. Murtha LA, McLeod DD, McCann SK, Pepperall D, Chung S, Levi CR, et al. Short-dura- tion hypothermia after ischemic stroke prevents delayed intracranial pressure rise. Int J Stroke 2014;9(5):553-9.
9. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. ‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 1996;53:309-15.
10. Murtha LA, McLeod DD, Pepperall D, McCann SK, Beard DJ, Tomkins AJ, et al. Intra- cranial pressure elevation after ischemic stroke in rats: cerebral edema is not the only cause, and short-duration Mild hypothermia is a highly effective preventive therapy. J Cereb Blood Flow Metab 2015;35(4):592-600.
11. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural his- tory of clinically identifiable subtypes of cerebral infarction. Lancet 1991;337: 1521-6.
12. Yang Y, Wang A, Zhao X, Wang C, Liu L, Zheng H, et al. The Oxfordshire community stroke project classification system predict clinical outcomes following intravenous thrombolysis: a prospective cohot study. Ther Clin Risk Manag 2016;12:1049-56.
13. Sung SF, Chen SC, Lin HJ, Chen CH, Tseng MC, Wu CS, et al. Oxfordshire community stroke project classification improves prediction of post-thrombolysis symptomatic intracerebral hemorrhage. BMC Neurol 2014;14:39.
14. Hansen HC, Helmke K. The subarachnoid spaces urrounding the optic nerves. An ul- trasound study of the optic nerve sheath. Surg Radiol Anat 1996;18(4):323-8.
15. Kimberly HH, Shah S, Marill K, Noble V. Correlation of optic nevre sheath diameter with direct measurement of intracranial pressure. Acad Emerg Med 2008;15:201-4.
16. Safak KY, Turkoglu O, Sencan BD, et al. Optik Sinir Kilifi Capi Olcumlerinde MRG ve USG Arasindaki Uyum. Okmeydani Tip Dergisi 2015;31(2):71-4.
17. Ropper AH, Shafran B. Brain edema after stroke. Clinical syndrome and intracranial pressure. Arch Neurol 1984;41:26-9.
18. Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypo- thermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29:2461-6.
19. Morley NC, Berge E, Cruz-Flores S, Whittle IR. Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev 2002;3:CD003435.
20. Young AM, Guilfoyle MR, Donnelly J, Scoffings D, Fernandes H, Garnett M, et al. Cor- relating optic nerve sheath diameter with opening intracranial pressure in pediatric traumatic brain injury. Pediatr Res 2016;81(3):443-7.
21. Bekerman I, Sigal T, Kimiagar I, Vaiman M. Initial evaluation of the intracranial pres- sure in cases of traumatic brain injury without hemorrhage. J Neurol Sci 2016;368: 285-9.
22. Bekerman I, Sigal T, Kimiagar I, Almer ZE, Vaiman M. Diagnostic value of the optic nerve sheath diameter in pseudotumorcerebri. J Clin Neurosci 2016;30:106-9.
23. Vaiman M, Sigal T, Kimiagar I, Bekerman I. Intracranial pressure assessment in trau- matic head injury with hemorrhage via optic nerve sheath diameter. J Neurotrauma 2016.