Download Interpretation of CUS and defining US findings. SOP: ePrime CP

ePrime
Interpretation of cranial ultrasound findings of
preterm infants at term age
SOP Reference: ePrime-CP-08/10/00
Departmental Responsibility: Paediatrics
Version Number: First Issue
Effective Date: 8 June 2010
Review by: David Edwards
Author: Phumza Nongena
Approved by: David Edwards
Version
Date
First Issue
8 June 2010
Date: 8 June 2010
Reason for Change
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TABLE OF CONTENTS
1.
PURPOSE .............................................................................................................................................. 3
2.
PERSONNEL & RESPONSIBILITIES ................................................................................................... 3
3.
BACKGROUND...................................................................................................................................... 3
4.
INTRODUCTION .................................................................................................................................... 3
5.
DEFINITIONS......................................................................................................................................... 4
6.
PROCEDURE ........................................................................................................................................ 5
7.
REFERENCES …………………………………………………………………………………………………...7
8.
APPENDICES .................................................................................................................................. …10
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1.
PURPOSE
The purpose of this SOP is to guide the Clinical Research Fellow (CRF or Neonatologist) on how
to give information to parents based on the head scan (cranial ultrasound) findings. It will as much
as possible give the parent/s prognostic information for their child based on the findings of the
ultrasound scan. The information given to parents will be based on best evidence there is on
ultrasound scan interpretation of preterm infants at term age equivalent.
2.
PERSONNEL & RESPONSIBILITIES
The Clinical Research Fellow (CRF or Neonatologist) will spend time communicating the
ultrasound findings to the parent/s.
3.
BACKGROUND
Preterm birth is the leading cause of perinatal morbidity in the developed world. In the United
Kingdom the preterm birth rate was last reported to be approximately 7% and
that of births before 32 completed weeks to be about 1.4% (1,2). With improvements in neonatal
care, the survival of extremely preterm infants has improved; however the reporting of neurological
sequelae rates especially cerebral palsy (CP) remains variable. Canada and Sweden report
improvements (3,4) and the reports from the EPICure
study are not that optimistic (5,6,7). Major neurodevelopmental sequelae are to a large degree
related to the occurrence of brain injuries, which is why brain imaging is central to neonatal
intensive care.
4.
INTRODUCTION
Since the late 1970s cranial ultrasound has been used for brain imaging in preterm infants (8).
Cranial ultrasound is commonly performed in most babies during their admission in a neonatal
intensive care unit. It is relatively cheap, safe and can be available at the cot side. It can be
performed by the attending paediatrician, neonatologist and paediatric radiologist. Although the
advantages of performing an ultrasound are numerous, it also has some limitations. Cranial
ultrasound is routinely performed through the anterior fontanelle which is optimal for supratentorial
structures, however this acoustic window is suboptimal for structures located further away from the
transducer (probe) as well as those embedded deep within the brain (9).
Other acoustic windows have been used by many in the quest to optimise ultrasound performance.
(9,10,11,12,13) In this study at least 2 acoustic windows will be used for scanning infants, however
reporting of the scan to parents and infant’s doctors will primarily be based on the anterior
fontanelle view results as this is the widely used and validated acoustic window.
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5.
DEFINITIONS
CRF: Clinical Research Fellow in this case the Neonatologist who will be responsible for
performing and giving the parents the results of the head scan.
Cerebral palsy (CP) : any one of a number of neurological disorders that appear in infancy
(including neonatal period) or early childhood and permanently affect body movement and muscle
coordination but don’t worsen over time. It can also be referred to as a group of non-progressive
and non-contagious motor conditions resulting in physical impairment or disability.
Cognitive function: intellectual process by which one becomes aware of, perceives, or
comprehends ideas. It involves all aspects of perception, thinking, reasoning, and remembering.
Cognitive impairment: also known as mental retardation is defined in the DSM-IV-TR as an
intelligence quotient (IQ) of approximately 70 or below with concurrent deficits or impairments in
adaptive functioning in at least 2 of the following areas: communication, self-care, home living,
social/interpersonal skills, use of community resources, self-direction, functional academic skills,
work, leisure, health, and safety; occurring before 18 years of age (14).
Neurodevelopmental impairment: psychomotor or mental impairments measured by one of a
number of instruments, for example psychomotor developmental index below 70 (PDI<70), mental
developmental index below 70 (MDI<70), developmental quotient below 85 as assessed by the
Griffiths developmental scale (GQ <85) or a mental processing composite score below 85
(MPC<85). Apart from Intelligence quotient of below 70 (IQ<70), MDI<70, DQ<85 and MPC<85
are other tools used to assess cognitive impairment.
Sensitivity: proportion of infants with disease (CP or cognitive impairment) who are correctly
identified by the test (ultrasound scan)
Specificity: proportion of infants without disease (CP or cognitive impairment) who are correctly
identified as such by the test (ultrasound scan)
Positive predictive value (PPV): proportion of test positive infants who truly have the disease (CP
or cognitive impairment)
Negative predictive value (NPV): proportion of test negative infants who truly do not have the
disease (CP or cognitive impairment)
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6.
PROCEDURE
Preamble: this study offers specialised head ultrasound and MRI at term, which is not currently
routinely offered in the NHS. This is because we don’t know which one is better in predicting the
infant’s neurodevelopmental outcome later on. What we know is that head scan (cranial
ultrasound) is not always correct and MRI might detect lesions of little or no significance. In
attempting to find which one is better at predicting outcome, images (whether ultrasound or MRI)
will be interpreted as seen; not interpreted to estimate previous lesion/s.
The findings will be interpreted as seen on the day and given in terms of real PPV with 95%
confidence limits for those who want specific numbers. This will be described to parents as a
percentage or fraction where appropriate. The interpretation of the findings will take into
consideration the overall risk of CP and cognitive impairment among preterm infants born before
33 weeks, which is about 9 and 32% respectively. [15] For CP, the risk will be divided into those
born before 28 weeks gestation and those born between 29 and 32 weeks gestation. A script of
how the imaging findings will be communicated to the parents is available on a separate SOP.
Ultrasound findings will be interpreted as follows:
6.1 Normal brain ultrasound:
When an ultrasound scan is normal we expect a vast majority of preterm infants to have normal
development (16,17,19,20,21,22,23,24).
(For parents who want more detail, a normal scan reduces the general risk that all preterm infants
have, and the chance of a major problem is as low as 4% and no higher than 9%)
Enlargement of the ventricles (moderate to severe ventricular dilation) without
visible blood:
When there is ventricular dilation at term not warranting intervention, we would expect 1/4 the
children to have problems such as cerebral palsy (17,18,20,21).
(For parents who want more detail, the risk major impairment (as defined in the meta-analysis) is
greater than 17% and could be as high as 28%)
6.2 Hydrocephalus or post haemorrhagic ventricular dilation:
When there is a massive enlargement of the ventricles, there is usually a build up of pressure
within the ventricles which often requires an intervention/s.
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In this case we would expect ½ the children to have difficulties with sitting, walking, concentration
on completion of tasks and later learning at school (20,21,25,26,27,28).
(For parents who want more detail, the risk of major impairment (as defined in the meta-analysis)
is greater than 1/4 and could be as high as 1/2. If hydrocephalus is not already known about by the
referring hospital and may need neurosurgical opinion explain that this is an unexpected finding
that might benefit from treatment and that we will urgently talk to referring hospital. Explain that will
unblind the MR data in the trial if the clinicians caring for the child need it)
6.3 Porencephalic cyst:
When a cyst develops anterior to the trigone, about 40 to 100% have a normal outcome. Cysts
further away from the trigone seem to be associated with the highest chance of normality and
those closer to it with the low chance of normal outcome (22,23).
(For parents who want more detail, at least 2/3 of children with an anterior lesion do not have
cerebral palsy, for a posterior lesion at least 2/3 do have cerebral palsy)
6.4 Cystic periventricular leukomalacia
Cystic leukomalacia usually appears on the scan about a few weeks after birth; it however is
associated with a poor prognosis.
When this condition is present, we would expect your child to have a high chance of having
cerebral palsy and cognitive impairment (16,19).
(For parents who want more detail, the scans are not precise in predicting the risk, but the chance
of having these problems is at least one in three, and perhaps as high as 9 out of 10)
6.5 Cerebellar injury: seen as bright echogenic lesions with the characteristics of
haemorrhage or atrophy if occurred earlier on
We are uncertain about the real impact of this; however there seems to be an increased chance of
difficulties with sitting, walking, concentration on getting tasks completed and learning at school,
but we cannot be precise (17,18).
(For parents who want more, it seems that there is probably about a 50% or better chance of
having a normal outcome)
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The lesions below (6.7 to 6.11) are not known to affect development in otherwise well infants who
are known to have a negative cytomegalovirus (CMV) screen.
6.6 Choroid plexus cyst/s:
There’s no data suggesting that it causes any problems
6.7 Germinal matrix cyst, subependymal, germinolytic, germinal matrix or layer,
pseudocysts:
These terms generally mean the same thing and are used for cysts seen within or adjacent to the
lateral walls of the anterior horns of the ventricles or in head of the caudate nuclei. There’s no data
suggesting that it causes any problems
6.8 Caudothalamic cysts:
These are seen in the notch between the thalamus and the head of the caudate nucleus. There’s
no data suggesting that these cause any problems.
6.9
Lenticulostriate vasculopathy (LSV):
Is defined as punctuate, linear or branching echogenic structures in the distribution of the
thalamo-striatal vessels within the basal ganglia and thalamus region.
6.10 Possible Calcifications
Will be defined as highly echogenic lesions within the white matter and/or basal ganglia with clear
margins. Withdraw from study and refer.
7. REFERENCES
1. Tucker J, McGuire W. Epidemiology of preterm birth. BMJ 2004;329:675-678
2. Hamilton BE, Miniño AM, Martin JA, Kochanek KD, Strobino DM, Guyer B. Annual Summary
of Vital Statistics: 2005. Pediatrics 2007;119;345-360
3. Himmelmann K, Hagberg G, Beckung E, et al. The changing panorama in of cerebral palsy in
Sweden.IX. Prevalence and origin in the birth year 1995-1998. Acta Paediatr 2005;94:287-94
4. Robertson CM, Watt MJ, Yasui Y. Changes in the prevalence of cerebral palsy for children
born very premature within a population-based programme over 30 years. JAMA
2007;297:2733-40
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5. Wood NS, Marlow N, Costeloe K, Gibson AT,Wilkonson AR. Neuro;ogic and developmental
disability after extremely preterm birth. EPICure study group.N Engl J Med 2000;343:378-84
6. Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and developmental disability at six
years of age after extremely preterm birth. N Engl J Med 2005;352:9-19
7. Johnson S, Hennessy EM, Smith R Ms, et al. Academic attainment and special educational
needs in extremely preterm children at 11 years of age: EPICure study. Arch Dis Child Fetal
Neonatal Ed 2009;94:F283-F289
8. Levene MI. Measurement of growth of the lateral ventricles in preterm infants with real-time
ultrasound. Arch Dis Child 1981;56:900-4
9. Van Wezel-Meijer. Neonatal cranial ultrasonography, 1
Heidelberg 2007
st
edition. Springer-Verlag Berlin
10. Correa F, Enriquez G, Rossello J,Lucaya J, Piqueras J, Aso C, et al. Posterior fontanelle
sonography: an acoustic window into the Neonatal Brain. Am J Neuroradiol 2004;25:12741282
11. Di Salvo. A new view of the neonatal brain: clinical utility of supplemental neurologic US
imaging windows. Radiographics 2001;21:943-955
12. Enriquez G, Correrrena F, Aso C, Carreno JC, Gonzalez R, Padilla NF, et al. Mastoid
fontanelle approach for sonographic imaging of the neonatal brain. Paediatr Radiol
2006;36:532-540
13. Luna JA, Goldstein RB. Sonographic visualization of neonatal posterior fossa abnormalities
through the posterolateral fontanelle. Am J Roentgenol 2000;174:561-567
14. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition, Text Revision. Washington, DC: APA Press; 2000:41-9.
15. Larroque B, Ancel P-Y, Marret S, et al. Neurodevelopmental disabilities special care of 5year-old children born before 33 weeks gestation (the EPIPAGE study): alongitudinal cohort
study. Lancet 2008;371:813-20
16. de Vries L. S. , Inge-Lot C, Van Haastert PPT, MA, Karin J. Radermaker K.J, Koopman C and
Groenendaal F. Ultrasound abnormalities preceeding cerebral palsy in high risk preterm
infants. Journal of Pediatrics, 2004; 144: 815-20
17. Kuban KCK, Allred EN, O’Shea TM, Paneth N, Pagano M, Dammann O, Leviton A, Du
Plessis A, Westra SJ, Miller CR, Bassan H, Krishnamoorthy K, Junewick J, Olomu N,
Romano E, Seibert J, Engelke S, Karna P, Batton D, O’Connor SE, and Keller CE, for the
ELGAN study investigators. Cranial ultrasound lesions in the NICU predict cerebral palsy at
age 2 years in children born at extremely low gestational age. J Child Neurol. 2009;24:63-72.
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18. O’Shea MT, Kuban CK, Allred NE, Paneth N, Pagano M, Dammann O, Bostic L Brooklier K,
McQuiston S, Miller A, Pasternak S, Plesha-Troyke S, Price J, Romano E, Solomon K.M,
Jacobson A, Westra S, Leviton A and for the Extremely Low Gestational Age Newborns Study
Investigators. Neonatal cranial ultrasound lesions and developmental delays at 2 years of
age among extremely low gestational age children. Pediatrics, 2008; 122: 662-669
19. Ancel P.Y, Livinec F., Larroque B, Marret S, Arnaud C, Pierrat V, Dehan M, N'Guyen S,
Escande B, Burguet A, Thiriez G, Picaud J-C, André M, Bréart G, Kaminski M and the
EPIPAGE Study Group. Cerebral palsy among very preterm children in relation to gestational
age and neonatal ultrasound abnormalities: The EPIPAGE Cohort Study. Paediatrics, 2006;
117: 828-835
20. Stewart A, Reynolds E, Hope P, et al. Probability of neurodevelopmental disorders estimated
from ultrasound appearance of brains of very preterm infants. Dev Med Child Neurol.1987; 29
:3 –11
21. Stewart A, Thorburn R, Hope P, Goldsmith M, Lipscomb A, Reynolds E. Ultrasound
appearance of the brain in very preterm infants and neurodevelopmental outcome at 18
months of age. Arch Dis Child.1983; 58 :598 –60
22. de Vries LS , Groenendaal F, Van Haastert IC, Eken P, Radermaker K.J, Meiners LC.
Asymmetrical myelination of the posterior limb of the internal capsule in infants with
periventricular haemorrhagic infarction: an early predictor of hemiplegia. Neuropediatrics
1999;30:315-319
23. Radermaker K.J, Groenendaal F, Jansen GH, Eken P, de Vries LS. U nilateral haemorrhagic
parenchymal lesions in the preterm infant: shape, site and prognosis. Acta Paediatrica
1994;83:602-608
24. Roelants-van Rijn AM, Groenendaal F, Beek FJA, Eken P, Van Haastert IC, de Vries LS.
Parenchymal brain injury in the preterm infant: comparison of cranial ultrasound, MRI and
neurodevelopmental outcome.
25. Ventriculomegaly trial group. Randomised trial of early tapping in neonatal posthaemorrhagic
ventricular dilation. Archives of diseases in childhood 1990;65:3-10
26. Whitelaw A, Jary S, Kmita G, Wroblewska J, Musialik-Swietlinska E, Mandera M, Hunt L,
Carter M, Pople I. Randomized Trial of Drainage Irrigation and Fibrinolytic Therapy for
Premature Infants with Posthemorrhagic Ventricular Dilatation: Developmental Outcome at 2
years. Pediatrics 2010;125(4):e852-e-858
27. International randomised controlled trial of acetazolamide and furosemide in post
haemorrhagic ventricular dilatation in infancy. International PHVD Drug Trial Group. Lancet
1998;352:433-40
28. Adams-Chapman I, Hansen NI, Stroll BJ, Higgins R. Neurodevelopmental outcome of
extremely low birth weights infants with post haemorrhagic hydrocephalus requiring shunt
insertion. Pediatrics 2008;121(5):e1167-e1177
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8. APPENDICES:
 Glossary
HPI
Haemorrhagic parenchymal infarct
c-PVL
Cystic periventricular leukomalacia
CP
Cerebral palsy
VD
Ventricular dilation
PHVD Post haemorrhagic ventricular dilation
IVH
Intraventricular haemorrhage
CA
Corrected age
DQ
Griffiths Developmental Quotient

Table of Risks
Table: Prediction of abnormal neuromotor function by cranial ultrasound
US test result
Cerebral Palsy
Pre-test
probability %
Normal scan
9
Grade 1 or 2 IVH
9
Grade 3 IVH
9
Grade 4 haemorrhage
(any)
Cystic PVL
9
Ventricular dilatation
9
Hydrocephalus
9
9
Likelihood
ratios
(95% CI)
0.5
(0.4-0.7)
1
(0.4-3)
4
(2-8)
11
(4-31)
29
(7-116)
3
(2-4)
4
(1-13)
Post test
probability %
(95% CI)
5
(4-6)
9
(4-22)
26
(13-45)
53
(29-76)
74
(42-92)
22
(17-28)
27
(10-56)
Heterogeneity
amongst studies
(I-squared %)
90
88
82
84
90
0
97
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Legend
Normal scan refers to absence of haemorrhage within the brain parenchyma or ventricles, cysts or
ventricular dilation. The grade of IVH (intraventricular haemorrhage) is given according to the Papile
classification. PVL= periventricular leukomalacia. Ventricular dilation = moderate to severe ventricular
dilation not meeting the criterion for hydrocephalus. Hydrocephalus = massive ventricular dilation >4
th
mm above the 97 centile. Pre-test probability refers to the prevalence of cerebral palsy based on the
Epipage study [15]. Likelihood ratio is the probability that a patient with cerebral palsy has a positive
test (abnormal US result). Post-test probability is the probability that a patient with a specific
abnormality on cranial ultrasound will have abnormal neuromotor function. Heterogeneity is a
measure of similarity between studies and the validity of statistical pooling.
Table: Cranial ultrasound to predict abnormal motor outcome in preterm infants by
gestational age (the Epipage study)
Gestational age
24–25
26
27
28
29
30
31
32
Risk of Cerebral palsy
18%
18%
12%
13%
12%
6%
9%
4%
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