Estimation of optic nerve sheath diameter on an initial brain computed tomography scan can contribute prognostic information in traumatic brain injury patients

Severe traumatic brain injury (TBI) is a leading cause of death and disability [1, 2]. A review of 23 surveys carried out in Europe estimated the annual incidence of TBI to be 235 per 100,000, with a mortality rate of about 15.4 per 100,000 - mainly due to motor vehicle accidents or falls [2]. In another recent survey, mortality in the United States was reportedly higher (18.4 per 100,000) [1]. Post-TBI disability is a major concern and its prevalence is probably underestimated. It is important to optimize the pre-admission care of TBI patients [3]. Improving a patient's overall prognosis requires mobilization of healthcare system human and material resources for the most seriously injured patients. Many factors have been reported to influence the prognosis of TBI, including age, gender, severity of injury, co-morbidities, concomitant use of anticoagulants, secondary insults, the initial Glasgow Coma Scale (GCS) score, the motor score, pupil reactivity, the type of lesion visualized on brain computed tomography (CT) scan, changes in intracranial pressure (ICP) and blood levels of specific proteins. Two prognostic scores for TBI patients on admission have been developed on the basis of the large, prospective IMPACT and CRASH databases [4, 5]. However, these scores are complex, require numerous data and are not easy to perform in the emergency unit. In this context, there is a need for a clearly relevant parameter with prognostic value for patients in the initial phase of TBI. The optic nerve sheath is the most accessible part of the brain meninges [6]. A strong relationship has been reported between optic nerve sheath diameter (ONSD, as evaluated by ultrasound) and ICP [7‐10]. Severe TBI patients admitted to the ICU generally undergo at least one initial brain CT scan. However, to the best of our knowledge, no study has focused on the initial ONSD measurement. The aim of the present study was therefore to evaluate the relationship between ONSD on the initial brain CT scan and the outcome of severe TBI patients admitted to the ICU.

Eighty-five adult TBI patients were admitted to the Amiens University Hospital ICU (Amiens, France) between October 2009 and July 2010. Four patients under the age of 18 were not included. Three individuals with traumatic orbital haematoma and one patient lacking an initial brain CT were excluded. A total of 77 patients were therefore included in the study (mean age: 43 ± 18; 81% males). TBI was mainly due to falls (47%) and motor vehicle accidents (43%). The time interval between trauma and the first brain CT was always < 3 hours. One-third of patients had a blood alcohol concentration over the legal limit in France. The mean ISS was 35 ± 15. One-third of patients had been initially treated in a primary care hospital. The initial GCS score was 7.2 ± 4.2. Twenty-four patients (31%) underwent neurosurgical evacuation of intracranial haematoma prior to admission to the neurosurgical ICU. Norepinephrine was administered in 13 patients (17%). The initial CT scan revealed traumatic, subarachnoid haemorrhage in 38 patients (49%), intraventricular haemorrhage in 13 patients (17%) and a midline shift in 30 patients (39%) and yielded a mean Marshall score of 3.8 ± 2.1. Invasive ICP monitoring was initiated in seven patients (9%). The mean length of stay in the ICU was 12 ± 14 days.

A strong relationship between CT signs suggestive of elevated ICP and ONSD values was observed: basal cisternal effacement: 7.5 ± 1.1 mm vs. 6.9 ± 0.9 (P = 0.02); midline shift ≥ 5 mm: 7.5 mm ± 0.9 vs. 6.8 ± 1.1 (P = 0.0002) and diffuse sulcal effacement: 7.4 mm ± 1.1 vs. 6.6 ± 0.9 (P = 0.001). A significant positive correlation was observed between ONSD and Marshall score (P = 0.01). ONSD was 7.6 mm ± 1.0 vs. 6.9 ± 1.0 (P = 0.01) in case of non-reactive pupils, 7.3 mm ± 1.1 vs. 6.9 ± 1.0 (P = 0.26) in the case of anisocoria and 7.6 mm ± 1.0 vs. 6.9 ± 1.1 (P = 0.03) in patients requiring surgical evacuation.

The ICU mortality rate was 28.6% (22 patients). Among the survivors, 46 were extubated (82%) and nine were tracheotomised (16%) during their stay in the ICU. The cause of death was brain death in 16 patients (72.7%), multiple organ failure in four (18.2%) and miscellaneous for two (9.1%). Demographic variables, TBI severity, clinical signs and outcomes are presented in Table 1. Briefly, non-survivors were older (P = 0.005), with a higher ISS (P = 0.02), a lower initial Glasgow Coma Scale (P = 0.03) and more frequent pupil reactivity abnormalities (P < 0.001). Initial brain CT scan results and clinical biochemical parameters are presented in Table 2. Compared with survivors, non-survivors presented more signs of intracranial hypertension, a higher incidence of subarachnoid haemorrhage (P = 0.04) and higher ONSD (6.8 ± 0.1 mm vs. 7.8 ± 0.1 mm, P < 0.001), as shown in Figure 2. A ROC curve was plotted to assess the prognostic value of ONSD (Figure 3). The area under the curve was 0.805 with a 95% CI of 0.694 to 0.883. A cutoff ≥ 7.3 mm had a sensitivity of 86.4% (65.1% to 97.1%), a specificity of 74.6% (61.0% to 85.3%), a positive predictive value of 57.6% (38.9% to 74.8%), a negative predictive value of 93.2% (81.3% to 98.6%), a positive likelihood ratio of 3.4 (2.7 to 4.3) and a negative likelihood ratio of 0.2 (0.1 to 0.6). Four parameters were independently associated with mortality: age > 32 years (AOR: 18.1, 95% CI: (1.6 to 201.2), P = 0.02), anisocoria on admission (AOR: 10.4; 95% CI: (1.6 to 65.1), P = 0.01), basal cistern compression on CT scan (AOR: 10; 95% CI: (1.9 to 53.4), P = 0.005) and ONSD ≥ 7.3 mm (AOR: 22.7; 95% CI: (3.2 to 159.6), P = 0.002). The Wald chi-square value for the model was 52.7 (df = 4, P = 0.0001). The goodness of fit of the model was not significant (Hosmer-Lemeshow chi-square = 3.9, ddl = 6, P = 0.69). The c-statistic of the model was 0.96 with 95% CI (0.92 to 0.99).

The GOS six months after discharge for the 55 ICU survivors was as follows: GOS 1 (n = 5, 9.1%), GOS 2 (n = 2, 3.6%), GOS 3 (17, 30.1%), GOS 4 (n = 13, 23.6%) and GOS 5 (n = 18, 32.7%). Overall six-month mortality in severe TBI was 35%. A statistically significant relationship was observed between GOS and initial ONSD measurement, as shown in Figure 4 (P = 0.03).

This study demonstrated a strong, independent relationship between ONSD on the initial brain CT scan and the mortality rate among severe TBI patients admitted to a neurosurgical ICU.

Mean ONSD in this study was much higher than that previously reported under various measuring conditions, even in patients with severe TBI. However, these results are in accordance with previous studies measuring ONSD on CT. The first study measured ONSD in 100 healthy volunteers [20] and found a mean ONSD of 4.4 mm with a 95% CI of 3.2 to 5.6. These values in healthy volunteers are higher than those proposed for the detection of elevated ICP by sonography. More recently, ONSD was evaluated on CT in normal-tension glaucoma patients compared to that of healthy volunteers [21] and revealed a mean ONSD of 8.0 ± 1.0 in normal-tension glaucoma patients and 6.2 ± 0.9 in healthy volunteers. Experimentally, in an optic nerve model obtained from cadaveric donors without neurological injury, a clear relationship was demonstrated between increased intracranial pressure and increased ONSD, but with ONSD values at 6.7 mm with higher pressures [22]. However, this study was purely experimental and was not conducted on injured patients under pathophysiological conditions. ONSD measurements have been more frequently reported with ultrasound. ONSD values greater than 7.0 mm have been reported in TBI patients with intracranial hypertension [23]. However, in a retrospective study, ONSD ≥ 5.0 mm was proposed to detect elevated ICP [24]. The inter-observer and intra-observer variations of ultrasound measurement of ONSD were recently calculated to be 0.5 mm and 0.2 mm, respectively [25]. These results are very similar to those reported in the present study based on CT measurement of ONSD. MRI has also been proposed to measure ONSD with a lower range of values than those reported in this study [18]. However, the limited accuracy of MRI with thicker brain slices may underestimate the real value of ONSD. With MRI measurement, errors have also been reported to be 1.3 to 1.5 mm [26]. One MRI study on ONSD in TBI patients with invasive ICP has been published [18]. The ONSD was significantly greater in TBI patients with raised ICP (> 20 mmHg; 6.31 +/- 0.50 mm) than in those with ICP of 20 mmHg or less (5.29 +/- 0.48 mm) or in healthy volunteers (5.08 +/- 0.52 mm). A study comparing MRI and B sonography in healthy subjects [27] showed that sonography underestimated ONSD: 5.72 mm (5.51 to 5.93) for MRI vs. 4.08 (3.4 to 4.3) for sonography. A recent evaluation of ONSD measured by MRI in astronauts exposed to microgravity reported ONSD values of 6.5 ± 1.0 mm [28]. The ONSD values measured by CT and MRI are higher than those reported with sonography. The ONSD measurements reported in the present study appear to be accurate in view of the low intra- and inter-observer variability determined prior to the study. A good correlation has been reported between CT scan and ultrasonography in healthy subjects [29]. However, the previous study overestimated ONSD by more than 10% with CT compared to sonography [29]. The mean ONSD in healthy subjects has been reported to be 5.5 mm [30], very close to the limit for elevated ICP reported for sonography [31], emphasising the differences in the measurements between these two methods.

Experimentally, Hansen et al. showed a correlation between ONSD and ICP and ICP variations [6, 9]. Other authors have used bedside transorbital sonography to assess ONSD in hydrocephalic patients [32]. Many researchers have investigated the significance of this parameter as a means of detecting intracranial hypertension [10, 17] in patients with TBI [8, 33], thereby allowing rapid triage in the emergency unit [34]. In the emergency department, an US evaluation of ONSD ≥ 5.0 mm was associated with CT findings of elevated ICP ([35]. A link between MRI-determined ONSD and elevated ICP has also been reported [18, 36]. However, to the best of our knowledge, no study has yet focused on brain CT scan that is routinely performed in severe TBI patients. ONSD is much easier to measure on CT scan than with sonography due to the good reproducibility of CT and the lack of a learning curve. Furthermore, with the development of telemedicine, tertiary reference centres now have access to the initial CT scan [37]. ONSD measurement may facilitate transfer decisions. The relationship between intracranial hypertension and prognosis has been widely demonstrated [38‐41]. Furthermore, ICP monitoring per se has never been found to be associated with improved outcomes in severe TBI patients [42] compared to clinical and radiological evaluation. When combined with other parameters, the initial measurement of ONSD may be clinically useful in the early diagnosis setting and to rapidly initiate aggressive treatment of suspected elevated ICP.

Interpretation of our data is subject to several limitations. First, the sample size may be considered to be small. We nevertheless included all consecutive patients over the study period. Some patients with less severe forms of TBI may have been hospitalized in primary care hospital ICUs without referral to our university hospital after CT imaging. In contrast, high-severity TBI patients rapidly progressing to brain death would not have been considered for transfer due to local multi-organ donation procedures. Although this aspect clearly constitutes a limitation, the measurement technique is very easy to implement and depends more on the software tools than the physician's ability. Furthermore, all brain CT scans are now performed in millimetre slices, enabling easy measurement of ONSD. The inter- and intra-observer variability of ONSD measurement was in accordance with the results reported in other studies, with very good reliability. Finally, the rate of ICP monitoring was very low in these severe TBI patients. This is another limitation of the study despite recent studies showing similar outcomes with ICP management versus clinical and radiological evaluation [42]. Brain CT scan ONSD measurements cannot be considered to be a monitoring tool for severe TBI patients. This study was not designed to evaluate this point, but only to consider available data before ICU admission. ONSD monitoring is much easier and less invasive by bedside sonography.

This study demonstrated a relationship between ONSD measured on the initial brain CT scan of severe TBI patients and ICU mortality rate. This simple, CT-based measurement could be of value in initial triage of severe TBI patients when transferring images from primary hospitals to reference centres. However, these results need to be validated in a larger cohort of patients.