Child's Nervous System

https://doi.org/10.1007/s00381-019-04235-8

FOCUS SESSION

Ultrasound non-invasive intracranial pressure

assessment in paediatric neurocritical care: a pilot study
Chiara Robba 1,2 & Danilo Cardim 3,4 & Marek Czosnyka 3,5 & Francisco Abecasis 6 & Stefano Pezzato 7 & Silvia Buratti 7 &
Andrea Moscatelli 7 & Cristina Sortica 8 & Fabrizio Racca 9 & Paolo Pelosi 2 & Frank Rasulo 10

Received: 20 May 2019 / Accepted: 27 May 2019

# Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract
Background The assessment of intracranial pressure (ICP) is essential in the management of neurocritical care paediatric patients.
The gold standard for invasive ICP is an intraventricular catheter or intraparenchymal microsensor but is invasive and carries
some risks. Therefore, a non-invasive method for measuring ICP (nICP) would be desirable especially in the paediatric popu-
lation. The aim of this study is to assess the relationship between ICP and different ultrasound–based methods in neurocritical
care paediatric patients.
Methods Children aged < 16 years with indication for invasive ICP monitoring were prospectively enrolled. The following non-
invasive methods were compared with the invasive gold standard: optic nerve sheath diameter ultrasound (ONSD)–derived nICP
(nICPONSD); arterial TCD–derived pulsatility index (PIa) and a method based on the diastolic component of the TCD cerebral
blood flow velocity and mean arterial blood pressure (nICPFVd).
Results We analysed 107 measurements from 10 paediatric patients. Results from linear regression demonstrated that, among the
nICP methods, ONSD has the best correlation with ICP (r = 0.852 (p < 0.0001)). Results from receiving operator curve analysis
demonstrated that using a threshold of 15 mmHg, ONSD has and area under the curve (AUC) of 0.94 (95% CI = 0.892–0.989),
with best threshold at 3.85 mm (sensitivity = 0.811; specificity = 0.939).
Conclusions Our preliminary results suggested that ONSD ultrasonography presents the best accuracy to assess ICP among the
methods studied. Given its non-invasiveness, repeatability and safety, this technique has the potential of representing a valid
option as non-invasive tool to assess the risk of intracranial hypertension in the paediatric population.

Keywords Optic nerve sheath diameter . Transcranial Doppler . Pulsatility index . Paediatric

* Chiara Robba 5
Institute of Electronic Systems, Warsaw University of Technology,
kiarobba@gmail.com Warszawa, Poland
6
1
Paediatric Intensive Care Unit, Centro Hospitalar Lisboa Norte,
Neurosciences Critical Care Unit, Addenbrooke’s Hospital, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK
7
2
Department of Anaesthesia and Intensive Care, S. Policlinico Neonatal and Pediatric Intensive Care Unit, Istuto G. Gaslini
Martino Hospital, IRCCS for Oncology and Neuroscience, Children’s Hospital, Genoa, Italy
University of Genova, Genoa, Italy
8
3 Neonatal Unit, The Rosie Hospital, Cambridge University Hospitals
Brain Physics Laboratory, Division of Neurosurgery, Department of NHS Foundation Trust, Cambridge, UK
Clinical Neurosciences, Addenbrooke’s Hospital, University of
Cambridge, Cambridge, UK 9
Pediatric Critical Care, S Antonio Cesare Arrigo Biagio,
4
Department of Anesthesiology, Pharmacology and Therapeutics, Alessandria, Italy
Vancouver General Hospital, University of British Columbia,
10
Vancouver, BC, Canada Department of Intensive Care, Spedali Civili Brescia, Brescia, Italy

Introduction
Intracranial hypertension (ICHP) is a devastating complica-
tion after brain injury, and its assessment is essential in the
management of acute intracranial catastrophe to limit or ac-
tively reduce it [13].
A frequent question in neurocritical care of children relates
to the indications and methods for ICHP measurement and
treatment. Direct measurement of intracranial pressure (ICP)
using an external ventricular drain (EVD) or intraparenchymal
ICP microsensor represents the gold standard for confirming
the presence of intracranial hypertension [15]. In children, the
simplest and longest-standing method of measuring ICP is to
perform a lumbar puncture (LP) and to observe the opening
and closing pressure. However, intracerebral probes have sev-
eral risks and complications and LP is an indirect and, at the
same time, imprecise procedure [2, 6, 21].
Therefore, invasive measurement of ICP is reserved for the
most severely affected children in whom the benefits of direct
measurement outweigh the risks of bleeding and infection
[13].
In this setting, a non-invasive method to assess ICP would
be crucial for the management of these patients. Despite sev-
eral authors attempted to find a non-invasive method to mea-
sure ICP, there is not currently an absolutely accurate method
available [32]. However, ultrasound-based non-invasive
methods are gaining interest and have shown promising re-
sults, especially in adult populations [22–27].
The aim of this study is to assess different ultrasound–
based methods to assess ICP non-invasively (nICP) by com-
paring them with the invasive gold standard in a paediatric
population. Using arterial transcranial Doppler ultrasonogra-
phy (TCD), we assessed the arterial pulsatility index (PIa) and
a method based on diastolic cerebral blood flow velocity
(FVd), even if it was not primarily intended to estimate ICP
but CPP. Using ultrasound, we assessed the optic nerve sheath
diameter (ONSD). Also, we aimed to test an ONSD-derived
formula for the assessment of ICP (nICPONSD), previously
described in the adult population [27].
Methods
The main institutional review board (IRB) of Alessandria
Paediatric Hospital, Italy, approved the study (entry code
ASO.RianPed.16.04). Detailed written informed consent was
provided to the family members (parents or legal tutors) re-
garding the study protocol, the scope of research and the safe-
ty of TCD examination.
Data were collected prospectively from children younger
than 16 years with severe brain injury requiring ICP monitor-
ing and admitted to the hospital between 1st July 2015 and 1st
January 2018. Exclusion criteria were the absence of an
Childs Nerv Syst
informed consent, a history of ocular pathology or optic nerve
trauma, skull base fracture with a cerebrospinal fluid (CSF)
leak and inaccessible ultrasound temporal window.
Demographic data, Glasgow Coma Scale (GCS) at admission
and the paediatric version of Glasgow Outcome Score (GOS-
E PEDS) [3] at discharge from intensive care unit were
recorded.
Ultrasound examinations
Ultrasound measurement was performed by a selected group
of trained operators (CR, FR, SP); the operators used a stan-
dardized insonation technique in order to reduce inter-operator
variability and were blinded to the patient’s clinical
background.
For each patient, we recorded bilateral middle cerebral ar-
tery (MCA) flow velocities (systolic [FVs], mean [FVm] and
FVd), ONSD and mean arterial pressure (ABPm) twice daily
(from day 1 to 5 post ICP probe insertion). Additional mea-
surements were performed in case of acute changes in ICP
(higher than 20 mmHg), as previously described [27]. The
final FV values were calculated as the average of the right
and left MCA measured values.
Transcranial Doppler examinations were performed using a
standard TCD machine with a 2-MHz probe as previously
described [25, 26]. Simultaneous measurements of ICP were
taken at the time of the study. All physiologic parameters were
kept stable during the TCD examination.
PIa was calculated according to Gosling’s method [16], and
FVd-derived formula was calculated according to Czosnyka
et al. (nICPFVd) [7].
A linear 7.5-MHz ultrasound probe was used to perform
ultrasound examination of the ONSD using a mechanical in-
dex (MI) below or at 0.3. Once the image was obtained, it was
frozen, the probe removed from the eyelid and all measure-
ments were subsequently performed. Ultrasound gel was ap-
plied on the surface of each eyelid. The probe was oriented
perpendicularly in the vertical plane and at around 30 degrees
in the horizontal plane on the closed eyelids of both eyes of the
patient. The measurements were made in both the axial and
sagittal planes 3 mm behind the retina in both eyes, and the
final ONSD value was calculated as the average of four mea-
sured values.
We took an average of 4 measurements per eye and then in
the next step the average of both eyes. Non-invasive ICP de-
rived from ONSD was estimated according to the regression
analysis between ICP and ONSD obtained from our previous
study in a cohort of adult TBI patients [27]:
nICPONSD ¼ 5  ONSD−13:92ðmmHgÞ
Childs Nerv Syst

Table 1 Characteristics of the patients included in the study. Abbreviations: F female, M male, ICH intracranial haemorrhage. TBI traumatic brain
injury. EVD external ventricular drain, GCS Glasgow Coma Scale, GOS-E Ped, Pediatric Glasgow Outcome Score

Patient 1 2 3 4 5 6 7 8 9 10
Sex F M M M F F M M M F
Age 7 5 8 10 11 14 7 4 5 9
Height (cm) 112 111 120 128 117 138 109 95 99 118
Weight (kg) 18 22 25 28 22 35 25 15 18 23
Reason for admission ICH TBI TBI TBI ICH ICH ICH ICH ICH ICH
Type of monitoring EVD Bolt Bolt Bolt EVD EVD Bolt EVD Bolt EVD
GCS at admission 5 3 4 6 3 3 4 4 6 3
GOS-E Ped 2 3 2 2 4 3 3 4 3 2

Statistical analysis
Statistical analysis of the data was conducted with R
Studio software (R version 3.1.2). Data were tested for
normal distribution using the Shapiro-Wilk test and are
presented as median (interquartile range [IQR]). All pa-
rameters assessed were non-parametric in nature.
Multiple measurements were considered as independent
values.
The correlations between direct ICP and the non-invasive
estimators were verified: ONSD, PI, nICPFVd using the
Spearman correlation coefficient (R, with the level of signifi-
cance set at 0.05).
The Bland-Altman method was used to determine the
agreement between invasive ICP and nICP estimation
methods, with 95% confidence interval for prediction
(CI) and bias [12]. The area under the curve (AUC)
of the receiver operating characteristic curve (ROC)
were performed to determine the ability of the best-
performing non-invasive method to detect raised ICP
(using a threshold of 15 and 20 mmHg).
Results
A total of 107 measurements from 10 consecutive pa-
tients were included in this study. One patient was ex-
cluded for the absence of informed consent. The char-
acteristics of the patients are described in Table 1.
Table 2 presents median (IQR) for the variables
assessed. Results from the regression analysis revealed
good correlation between invasive ICP and ONSD, r
(Spearman) = 0.852 (p < 0.0001) (Fig. 1). The use of
the nICPONSD produced the same correlation coefficient
as ONSD itself (r = 0.852, p < 0.0001), although the
formula resulted in an underestimation of ICP. A signif-
icant but not strong correlation was also found between
nICPFVd formula and ICP: (r = 0.441, p < 0.0001) and
PIa and ICP (r = 0.321, p < 0.001).
Figure 2 shows the behaviour of ICP and ONSD for each
patient during the study. Bland-Altman analysis using
nICPONSD formula found a bias of − 5.93 mmHg, with 95%
confidence interval (CI) for ICP prediction of ±8.33 mmHg.
nICP FVd had a bias of 7.91 mmHg and a 95% CI of
±16.26 mmHg (Fig. 3).
Results from ROC analysis demonstrated that using a
threshold of 15 mmHg, ONSD had AUC of 0.94 (95% CI =
0.892–0.989), with best threshold at 3.85 mm (sensitivity =
0.811; specificity = 0.939). Considering a threshold of
20 mmHg, AUC was 0.976 (95% CI = 0.948–1.00), with best
threshold at 4.75 mm (sensitivity = 0.956; specificity = 0.938)
(Fig. 4).
Discussion
According to our results, in the paediatric population, ONSD
appears as the best estimator of ICP compared to the other
methods. At our knowledge, this is the first report comparing
different non-invasive ultrasound–based methods with simul-
taneous direct ICP measurements in a paediatric population.
Similarly to our results, in our previous study in an adult
cohort of TBI patients, we found that ONSD had a good cor-
relation with invasive ICP, whilst PI and nICPFVd had poor
correlation with ICP [27].
An elevation in intracranial pressure can be a surgical or
medical emergency [30]. A recent study [10] demonstrated that
the magnitude and the duration of ICP insult, called ‘dose of
ICP’ concept is strongly correlated with the patients’ outcome
in both the paediatric and the adult population. In this study, the
transition curve of ICP, considering the duration and the inten-
sity of the insult for the paediatric cohort, resembled that of
adults. This finding indicated that in children, episodes of lower
intensity and shorter duration of intracranial hypertension are
associated with worse outcomes compared to adults. Also, in
children, the exponential decay transition curve approximates
the vertical 10-mmHg line, and above 20 mmHg, the associa-
tion with worse outcome occurs within 8 min.
 Childs Nerv Syst

Table 2 Median (IQR) current guidelines are not clear about indications for in-
values of the assessed
vasive ICP measurements. In adults, the latest Brain
variables. ICP intracra-
nial pressure, ABPm Trauma Foundation guidelines [5] have downgraded pre-
mean arterial blood pres- vious recommendations on ICP monitoring, as evidence
sure, ONSD optic nerve ICP (mmHg) 11.00(15.5–6.60) did not meet current standards anymore, and the lack of
sheath diameter, ABPm mmHg 61.00(71.00–52.50) clear indications on ICP monitoring causes significant dif-
nICPONSD non-invasive ONSD mm 3.70(4.50–3.40)
estimator of ICP based ferences in the clinical practice among centres. For chil-
on ONSD, nICPFVd non- nICPONSD mmHg 4.66(8.58–3.19) dren, guidelines suggest ICP monitoring in severe TBI
invasive estimator of ICP nICPFVd mmHg 16.93(22.11–13.84) patients with low GCS (≤ 8), and also highlight the im-
based on FVd, PI PIa 0.82(1.15–0.68)
pulsatility index
portance of ICP monitoring in conscious children at risk
for neurologic deterioration as a result of traumatic mass
lesions, or in whom serial neurologic examination is pre-
cluded (sedation, neuromuscular blockade or anaesthesia)
There are many possible conditions that can determine [13].
elevated ICP in children, including traumatic brain injury, The gold standard for ICP measurement is an external
intracerebral haemorrhage, shunt insertion or malfunction, ventricular drain or an intraparenchymal probe [28, 32].
arachnoid cyst and craniosynostosis [32]. However, However, invasive monitoring carries several risks

Figure 1 Scatterplots of the linear relationship between intracranial c Estimator based on the diastolic cerebral blood flow velocity (nICPFVd
pressure (ICP) and different non-invasive ICP estimators. a Optic nerve (mmHg), r = 0.441 [p < 0.0001]). d Pulsatility index (PIa (a.u.), r = 0.321
sheath diameter (ONSD (mm), r = 0.852 [p < 0.0001]). b ONSD-derived [p < 0.001]). Light grey shaded areas on the plots represent the 95%
non-invasive ICP method (nICPONSD (mmHg)), r = 0.852 [p < 0.0001]). prediction interval for the linear regressions
Childs Nerv Syst

Figure 2 Behaviour over time of ONSD (in mm, black line) and invasive ICP (in mmHg, grey line) for each patient included in the analysis

including bleeding and infection [2, 21] which preclude
their use in some clinical condition (like coagulopathy).
Moreover, there are several scenarios where invasive ICP
monitoring is not indicated, but a nICP assessment would
be useful (e.g. mild or moderate traumatic brain injury,
meningitis, hydrocephalus, metabolic coma).
Various methods for nICP monitoring have been described
in adult and paediatric populations [23, 32]. Among these,
ultrasound-based non-invasive methods are gaining populari-
ty as they are safe, easily available and low cost.
TCD assessment of the cerebral blood flow velocity in the
basal cerebral vessels has long been used as a non-invasive
surrogate measure of cerebral blood flow and ICP. Pulsatility
index has been one of the most used TCD-derived nICP esti-
mation methods. Some authors have reported strong associa-
tion between PI and ICP [4]; however, such findings have not
been replicated by other studies, which reported poor correla-
tions between these parameters in adult TBI populations [8,
27, 33].
There are few reports on the relationship between PI and
ICP in children with TBI. Figaji et al. [9] in a cohort of 34
children found a weak relationship between mean values of
ICP and PI (r = 0.36, p = 0.04). Similarly, our findings dem-
onstrate that PI was not strongly correlated with ICP. In ex-
perimental models of intracranial hypertension, nICPFVd has
shown promising results [28], and in a recent pilot study

Figure 3 Bland-Altman plots for different non-invasive ICP methods. a nICPONSD formula shows a bias of − 5.93 mmHg, with 95% CI for ICP
prediction of ±8.33 mmHg. b nICPFVd demonstrated a bias of 7.91 mmHg with 95% CI of ±16.26 mmHg.

Figure 4 Receiver operating characteristic (ROC) analysis for optic
nerve sheath diameter method (ONSD). The values shown on the curve
in a and b panels represent the best thresholds (cut-off values presenting
Rasulo et al. [22] demonstrated in a cohort of 38 adult brain–
injured patients that nICPFVd may accurately exclude intracra-
nial hypertension in patients with acute brain injury, showing
a sensitivity of 100% and a specificity of 91.2% for a threshold
of 20 mmHg. In our group of patients, we found a significant
but weak correlation between nICPFVd and ICP; however, at
our knowledge, our study is the first one assessing this esti-
mation method in children and needs further validation.
The optic nerve is part of the central nervous system. A rise
in ICP causes an increase of the diameter of the perioptic
subarachnoid space within the dural optic nerve sheath
(ONS), which leads to an increase in optic nerve sheath diam-
eter (ONSD) [24, 29]. Transorbital sonography represents a
potentially useful and safe method to measure the ONSD for
rapid diagnosis of ICHP in infants.
The upper limit of the normal range for optic nerve sheath
diameter is 4.5 mm in patients over 1 year of age, and 4 mm in
children. In a study including healthy volunteers, the range of
ONSD was 2.1–4.3 mm (mean 3.08 ± 0.36), suggesting that
an ONSD greater than 4 mm in infants younger than 1 year
old, and ONSD ≥ 4.5 mm in older children, should be consid-
ered abnormal [1]. In adults, the threshold of ONSD is be-
tween 5 and 6 mm, and this might explain why the use of
nICPONSD estimation formula previously described in an adult
population results in underestimation of the ICP prediction in
children [ 11, 17, 18, 27, 31].
This discrepancy of our ONSD values compared to previ-
ously published values [1] might be the result of a low reso-
lution of ultrasound transducer used in our study (just
7.5 MHz), since most authors more recently have used >
10 MHz.
The application of ONSD in children has been investigated
in different clinical scenarios associated with intracranial hy-
pertension, such as acute hydrocephalus [14, 17, 18].
Childs Nerv Syst
the best sensitivity and specificity [in brackets]) for prediction of intra-
cranial hypertension (ICP) > 15 mmHg (a) and > 20 mmHg (b). AUC is
presented followed by 95% confidence intervals
Padayachy et al. [19, 20] reported a good correlation between
ONSD and ICP in a cohort of brain-injured paediatric patients
(r = 0.66, p < 0.001), with excellent repeatability and intra-
observer variability (α = 0.97–0.99). Testing for inter-
observer variability revealed also good correlation [14, 19].
However, a limitation of that study was that ONSD measure-
ment was performed prior to invasive measurement of ICP.
In our report, ONSD showed an even better association
with ICP, comparable with the results previously described
in the adult population [27]. Furthermore, ONSD in the pae-
diatric population also had the best accuracy when compared
with TCD-derived nICP methods.
We tried to apply our formula validated in a cohort of adult
brain–injured patients for the direct estimation of ICP
(ICPONSD). As shown in Fig. 2, there is a large variability of
ICP and ONSD within the 10 patients. Also, our results show
that there is an underestimation of about 6 mmHg by the
formula (bias of − 5.93 mmHg). These preliminary data show
that a formula cannot be easily transferred from one cohort to
another (especially different populations) and should not be
used in the paediatric clinical practice.
Furthermore, it can be inferred from the repeated measure-
ments of ICP/ONSD in 10 patients that the ICP/ONSD rela-
tionship is highly individual. Therefore, our understanding is
that a formula could be valid for an individual, but not for an
entire cohort.
Limitations
There are several limitations that need to be mentioned.
This is an observation pilot study whose major limita-
tion is the very small sample size. Further prospective
studies with a larger number of patients will be needed
to confirm these preliminary results.
Childs Nerv Syst
Moreover, cerebral blood flow velocity measurements
using TCD were not continuous, precluding the assessment
of nICP changes in time domain 23,27.
Finally, most of our measurements were obtained in pa-
tients with relatively well-controlled ICP. Also, larger valida-
tion studies containing a wider range of intracranial pressure
values will be required to assess and validate these results
before introduction of ONSD for nICP estimation in paediatric
clinical practice.
Conclusion
Non-invasive ICP assessment using ultrasound methods are
an attractive option in the paediatric population. These
methods are quick, safe, repeatable and allow bedside moni-
toring in different clinical scenarios (neurocritical and general
intensive care, operating room, emergency department).
In this preliminary report, we found that among the studied
methods, ONSD presented the best accuracy when compared
with other TCD-derived nICP methods and could potentially
be useful as non-invasive screening tool when invasive
methods are not available or contraindicated. However,
ONSD has several limitations and further studies will be need-
ed to confirm our results and assess its role in paediatric clin-
ical practice.
Acknowledgements DC and MC are partially financially supported by
NIHR BRC Cambridge, UK, and DC is financially supported by a
Cambridge Commonwealth European & International Trust scholarship.
For the remaining authors, none was declared.
Compliance with ethical standards
Funding None.
Conflict of interest None.
References
1. Ballantyne J, Hollman AS, Hamilton R, Bradnam MS, Carachi R,
Young DG, Dutton GN (1999) Transorbital optic nerve sheath ul-
trasonography in normal children. Clin Radiol 54:740–742
2. Bauer DF, Razdan SN, Bartolucci AA, Markert JM (2011) Meta-
analysis of hemorrhagic complications from ventriculostomy place-
ment by neurosurgeons. Neurosurgery 69:255–260
3. Beers SR, Wisniewski SR, Garcia-Filion P, Tian Y, Hahner T,
Berger RP et al (2012) Validity of a pediatric version of the
Glasgow Outcome Scale–extended. J Neurotrauma 29:1126–1139
Available: http://online.liebertpub.com/doi/abs/10.1089/neu.2011.
2272
4. Bellner J, Romner B, Reinstrup P, Kristiansson KA, Ryding E,
Brandt L (2004) Transcranial Doppler sonography pulsatility index
(PI) reflects intracranial pressure (ICP). Surg Neurol 62:45–51
5. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GWJ,
Bell MJ, et al: Guidelines for the Management of Severe
Traumatic Brain Injury, Fourth Edition Neurosurgery 0:1–10, 2016
6. Czosnyka M (2004) Monitoring and interpretation of intracranial
pressure. J Neurol Neurosurg Psychiatry 75:813–821 Available:
http://jnnp.bmj.com/cgi/doi/10.1136/jnnp.2003.033126
7. Czosnyka M, Matta BF, Smielewski P, Kirkpatrick PJ, Pickard JD
(1998) Cerebral perfusion pressure in head-injured patients: a non-
invasive assessment using transcranial Doppler ultrasonography. J
Neurosurg 88:802–808
8. De Riva N, Budohoski KP, Smielewski P, Kasprowicz M, Zweifel
C, Steiner LA et al (2012) Transcranial doppler pulsatility index:
what it is and what it isn’t. Neurocrit Care 17:58–66
9. Figaji AA, Zwane E, Fieggen AG, Siesjo P, Peter JC (2009)
Transcranial Doppler pulsatility index is not a reliable indicator of
intracranial pressure in children with severe traumatic brain injury.
Surg Neurol 72:389–394. https://doi.org/10.1016/j.surneu.2009.02.
012
10. Güiza F, Depreitere B, Piper I, Citerio G, Chambers I, Jones PA, Lo
TYM, Enblad P, Nillson P, Feyen B, Jorens P, Maas A, Schuhmann
MU, Donald R, Moss L, van den Berghe G, Meyfroidt G (2015)
Visualizing the pressure and time burden of intracranial hyperten-
sion in adult and paediatric traumatic brain injury. Intensive Care
Med 41:1067–1076
11. Helmke K, Hansen HC (1996) Fundamentals of transorbital sono-
graphic evaluation of optic nerve sheath expansion under intracra-
nial hypertension. I. Experimental study. Pediatr Radiol 26:701–
705
12. Hosmer D, Lameshow S (1989) Applied logistic regression. Wiley,
New York
13. Kochanek PM, N a C, Adelson PD, Ashwal S, Bell M, Bratton SL
et al (2012) Guidelines for the acute medical management of severe
traumatic brain injury in infants, children, and adolescents - second
edition. Pediatr Crit Care Med 13(Suppl):S1–S82 Available: https://
www.braintrauma.org/uploads/08/08/guidelines_pediatric2_2.pdf
14. Le A, Hoehn ME, Smith ME, Spentzas T, Schlappy D, Pershad J
(2009) Bedside sonographic measurement of optic nerve sheath
diameter as a predictor of increased intracranial pressure in children.
Ann Emerg Med 53:785–791
15. Luerssen TG (1997) Intracranial pressure: current status in moni-
toring and management. Semin Pediatr Neurol 4:146–155
16. Michel E, Zernikow B (1998) Gosling’s Doppler pulsatility index
revisited. Ultrasound Med Biol 24:597–599
17. Newman WD (2002) Measurement of optic nerve sheath diameter
by ultrasound: a means of detecting acute raised intracranial pres-
sure in hydrocephalus. Br J Ophthalmol 86:1109–1113 Available:
http://bjo.bmj.com/cgi/doi/10.1136/bjo.86.10.1109
18. Oestreich AE (2006) Sonographic evaluation of optic nerve diam-
eter in children with raised intracranial pressure. Yearb Diagnostic
Radiol 2006:180–181 Available: http://linkinghub.elsevier.com/
retrieve/pii/S0098167208703709
19. Padayachy LC, Padayachy V, Galal U, Gray R, Fieggen AG (2016)
The relationship between transorbital ultrasound measurement of
the optic nerve sheath diameter (ONSD) and invasively measured
ICP in children: part I: repeatability, observer variability and general
analysis. Childs Nerv Syst 32:1769–1778
20. Padayachy LC, Padayachy V, Galal U, Pollock T, Fieggen AG
(2016) The relationship between transorbital ultrasound measure-
ment of the optic nerve sheath diameter (ONSD) and invasively
measured ICP in children. Childs Nerv Syst 32:1779–1785
21. Poca M-A, Sahuquillo J, Arribas M, Báguena M, Amorós S, Rubio
E (2002) Fiberoptic intraparenchymal brain pressure monitoring
with the Camino V420 monitor: reflections on our experience in
163 severely head-injured patients. J Neurotrauma 19:439–448
Available: http://www.ncbi.nlm.nih.gov/pubmed/11990350

22. Rasulo FA, Bertuetti R, Robba C, Lusenti F, Cantoni A, Bernini M,
Girardini A, Calza S, Piva S, Fagoni N, Latronico N (2017) The
accuracy of transcranial Doppler in excluding intracranial hyperten-
sion following acute brain injury: a multicenter prospective pilot
study. Crit Care 21:44 Available: http://ccforum.biomedcentral.
com/articles/10.1186/s13054-017-1632-2
23. Robba C, Bacigaluppi S, Cardim D, Donnelly J, Bertuccio A,
Czosnyka M (2015) Non-invasive assessment of intracranial pres-
sure. Acta Neurol Scand
24. Robba C, Donnelly J, Bertuetti R, Cardim D, Sekhon MS, Aries M,
Smielewski P, Richards H, Czosnyka M (2015) Doppler non-
invasive monitoring of ICP in an animal model of acute intracranial
hypertension. Neurocrit Care 23:419–426
25. Robba C, Cardim D, Donnelly J, Bertuccio A, Bacigaluppi S,
Bragazzi N et al (2016) Effects of pneumoperitoneum and
Trendelenburg position on intracranial pressure assessed using dif-
ferent non-invasive methods. Br J Anaesth 117:783–791 Available:
http://bja.oxfordjournals.org/lookup/doi/10.1093/bja/aew356
26. Robba C, Bragazzi L, Bertuccio A, Cardim D, Donnelly J, Sekhon
M et al (2016) Effects of prone position and positive end-expiratory
pressure on noninvasive estimators of ICP : a pilot study. J
Neurosurg Anesth:1–8
27. Robba C, Cardim D, Tajsic T, Pietersen J, Bulman M, Donnelly J,
Lavinio A, Gupta A, Menon DK, Hutchinson PJA, Czosnyka M
(2017) Ultrasound non-invasive measurement of intracranial pres-
sure in neurointensive care: a prospective observational study.
PLoS Med 14:e1002356
28. Robba C, Santori G, Czosnyka M, Corradi F, Bragazzi N,
Padayachy L, Taccone FS, Citerio G (2018) Optic nerve sheath
diameter measured sonographically as non-invasive estimator of
Childs Nerv Syst
intracranial pressure: a systematic review and meta-analysis.
Intensive Care Med 44(8):1284–1294
29. Robba C, Goffi A, Geeraerts T, Cardim D, Via G, Czosnyka M,
Park S, Sarwal A, Padayachy L, Rasulo F, Citerio G (2019) Brain
ultrasonography: methodology, basic and advanced principles and
clinical applications. A narrative review. Intensive Care Med
30. Stocchetti N, Maas AIR (2014) Traumatic intracranial hyperten-
sion. N Engl J Med 370:2121–2130 Available: http://www.nejm.
org/doi/abs/10.1056/NEJMra1208708
31. Tsung J, Blaivas M, Cooper A, Levick N (2005) A rapid noninva-
sive method of detecting elevated intracranial pressure using bed-
side ocular ultrasound: application to 3 cases of head trauma in the
pediatric emergency department. Pediatr Emerg Care 21:94–98
Available: http://journals.lww.com/pec-online/Abstract/2005/
02000/A_Rapid_Noninvasive_Method_of_Detecting_Elevated.4.
aspx
32. Wiegand C, Richards P (2007) Measurement of intracranial pres-
sure in children: a critical review of current methods. Dev Med
Child Neurol 49:935–941
33. Zweifel C, Czosnyka M, Carrera E, De Riva N, Pickard JD,
Smielewski P (2012) Reliability of the blood flow velocity
pulsatility index for assessment of intracranial and cerebral perfu-
sion pressures in head-injured patients. Neurosurgery 71:853–861
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.