Focal Ischemic Cerebral Injury in the Newborn: Diagnosis by Ultrasound and Correlation with Computed Tomographic Scan

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Focal lschemic

Cerebral

Injury

in the Newborn:

Diagnosis

by Ultrasound

and Correlation

with

Computed

Tomographic

Scan

Alan

Hill, MD, PhD,

David

J. Martin,

MB, Alan

Daneman,

MB, and

Charles

R. Fitz,

MD

From the Departments of Pediatrics and Radiology, The Hospital for Sick Children, University of Toronto, Toronto

ABSTRACT. Ischemic brain injury in the newborn is a common cause of subsequent neurologic deficits seen in

older children. Clearly, determination of severity and

location of such injury is important for management and

prognosis. Although ultrasound scanning of the brain has

been used extensively in the premature infant for

diag-nosis of hemorrhagic lesions, its use in the term infant

for recognition of isehemic cerebral lesions has not been

reported. Four cases are described in which focal

echo-dense areas were identified on ultrasound scan of the

brain. These echodense areas on ultrasound corresponded

to the appearance on computed tomographic (CT) scan of areas of decreased density which are known to

repre-sent ischemic cerebral injury. In three of the four cases

there were focal neurologic findings and/or focal abnor-malities on EEG. In two cases, real-time ultrasound

scanning demonstrated changes in arterial pulsations in

cerebral vessels in the area of the lesions. Thus in both,

there was diminution in pulsations within the echodense

areas and in one case, an increase in pulsations was

observed at the periphery of the echodense lesion. Our

data demonstrate the value of ultrasound scanning for

assessment of the extent and location of focal cerebral

ischemic lesions in the newborn. Such assessment per-mite assessment ofprognosis. Pediatrics 1983;71:790-793;

focal cerebral injury, newborn, ultrasound.

Perinatal hypoxic-ischemic cerebral injury is the most common cause of subsequent nonprogressive neurologic handicap (eg, cerebral palsy, mental re-tardation, seizures) seen in older children.’ Clearly, determination of the extent and distribution of cerebral injury is of major importance for manage-ment and prognosis. The severity of

hypoxic-is-Received for publication July 9, 1982; accepted Sept 28, 1982.

Reprint requests to (A.H.) Department of Pediatrics, University

Hospital, Saskatoon, Saskatchewan, Canada S7N OXO.

American Academy of Pediatrics.

chemic injury may be assessed to some extent by consideration of the history and neurologic exami-nation. In addition, investigations such as lumbar puncture, electroencephalography, technetium

brain scan, and, more recently, computed

tomo-graphic (CT) scan may provide valuable informa-tion.

Ultrasound scanning of the brain has been used extensively in the premature infant for the diag-nosis of periventricular/intraventricular

hemor-23 and other hemorrhagic lesions.4 However,

its use in the term infant for recognition of ischemic lesions has not been reported.

In this communication, we describe, in the new-born, the appearance on ultrasound scan of focal

echodense areas (presumably nonhemorrhagic is-chemic lesions) and the correlation of such lesions with focal areas of low density on CT scan.

METHODS

Compound B static ultrasound scans were ob-tamed with a Unirad EDP 1000 scanner with 5-MHz short-focus, 6-mm diameter transducer. Real-time ultrasound scans were obtained with a Tech-nicare auto sector scanner with 5-MHz transducer. Coronal and parasagittal images were obtained through the anterior fontanel.

CASE REPORTS

Case I

This patient was born at 41 weeks of gestation to a 17-year-old gravida 1 para 0 following an uneventful preg-nancy. Birth weight was 3,050 g and Apgar scores were 1 and 5 at one and five minutes, respectively. Thick me-conium was noted. A generalized seizure occurred at 21 hours of age, at which time the blood glucose level was

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sei-ARTICLES 791 zures continued and treatment with phenobarbital (20

mg/kg) was begun. The infant was transferred to The

Hospital for Sick Children (Toronto) at age 7 days

be-cause of marked jitteriness and intermittent generalized seizures. Physical examination revealed an alert and ac-tive infant who was markedly jittery. Results of cranial

nerve examination were normal. Spontaneous movement

of extremities was equal bilaterally, deep tendon reflexes

were brisk and symmetrical, and there was sustained

clonus at each ankle. Treatment with phenobarbital was

continued and there were no further seizures. An EEG at

age 7 days showed spike discharges arising from the left

hemisphere. On day 8 an ultrasound scan of the head in

coronal plane showed an area of increased echoes in the

left hemisphere (Fig 1, left). A CT scan of the head on day 17 showed a large low-density area in the same area

of the left hemisphere (Fig 1, right). The remainder of the hospital course was unremarkable and at the time of

discharge at age 17 days, neurologic examination

cbs-closed no abnormalities.

Case 2

This infant was born at 40 weeks of gestation to a

24-year-old gravida 1 para 0 following an uneventful

preg-nancy. Labor was prolonged and delivery included the

use of midforceps. Birth weight was 3,520 g and the Apgar

score was 8 at one minute. During the first three days of

life there were several cyanotic episodes and the infant

was transferred to The Hospital for Sick Children. On

admission subtle seizures occurred and were treated with phenobarbital. The infant was active and alert. There was a large cephalohematoma in the right parietal region and a mild right facial weakness. Examination of the motor system revealed mild hypotonia and the deep ten-don reflexes were 1+ and symmetrical. An EEG

con-tamed seizure activity in the left hemisphere. Seizures ceased on the second day of hospitalization. A CT scan

of the head on day 6 of life showed a large area of

decreased density in the distribution of the left middle cerebral artery (Fig 2, left). An ultrasound scan of the

Fig 1. Left, Ultrasound scan in anterior coronal plane

at age 8 days. Note areas of increased echoes in left frontoparietal areas (arrows). Right, Computed

tomo-graphic scan (age 17 days) superior to lateral ventricles.

Note area of decreased density in left frontoparietal

re-gion.

Fig 2. Left, Computed tomographic scan on day 6 of life

shows area of decreased density in distribution of left

middle cerebral artery. Right, Coronal ultrasound scan at

age 10 days shows area of increased echoes on left

sur-rounding Sylvian fissure (arrow).

head on day 10 showed an extensive area of increased

echoes in the same region of the left hemisphere (Fig 2,

right). In the affected region, pUlsations of the middle

cerebral artery could not be detected. However,

pulsa-tions of the right middle cerebral artery were seen clearly. At the time of discharge on day 11 of life, neurologic

examination revealed a mild right hemiparesis.

Case 3

This patient was born to a 31-year-old gravida 2 para 1 following a pregnancy that was complicated by

gesta-tional diabetes and oligohydramnios. Polycystic kidneys

were diagnosed by ultrasound examination 23 days prior to delivery. The infant was delivered by cesarean section

at 37 weeks of gestation. Birth weight was 4,960 g and

Apgar scores were 7 and 8 at one and five minutes,

respectively. At birth the infant was alert and active with

mild tachypnea and indrawing. The abdomen was

dis-tended by two large masses which occupied each flank

region. Extremities moved symmetrically, and the deep

tendon reflexes were symmetrical. Ultrasound

examina-tion of the abdomen revealed polycystic kidneys. Over the next 25 days there was renal failure, hypertension,

and nutritional problems. On day 26 of life, examination

revealed an alert and active infant. Head circumference

was 36 cm and the anterior fontanel was soft and flat.

Cranial nerve examination was normal. The tone was

increased symmetrically, deep tendon reflexes were

sym-metrical, and the grasp and Moro reflexes were

symmet-rical. Findings from an EEG on day 20 were normal. A CT scan of the head on day 30 revealed a large area of

decreased density in the distribution of the left middle

cerebral artery (Fig 3, left). Ultrasound examination of

the head on day 41 showed areas of increased echoes in

the left hemisphere (Fig 3, right) corresponding to the area of decreased density noted on CT scan. The infant was discharged on day 56, at which time there were no focal neurologic abnormalities.

Case 4

This patient was born at term to a 30-year-old gravida

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Fig 3. Left, Computed tomographic scan at 30 days of

age. Note area of decreased density in distribution of left

middle cerebral artery. Right, Ultrasound scan (41 days of age) in posterior coronal plane at level of trigone. Note

area of increased echoes in left hemisphere (arrow). Areas

of increased echoes (C) represent choroid plexus.

1 para 0 following a pregnancy that was uncomplicated until the time of delivery. Membranes were ruptured 48

hours prior to delivery and maternal fever was treated

with ampicillin and gentamycin. At delivery the amniotic

fluid was foul smelling and meconium stained. Delivery was vaginal in the vertex position. Birth weight was 3,750 g and Apgar scores were 7 and 10 at one and five minutes,

respectively. Blood glucose estimation (by Dextrostix)

was zero, and the infant was treated immediately with

intravenous glucose. The infant was transferred to The

Hospital for Sick Children. Following septic work-up, treatment with ampicillin and chloramphenicol was be-gun. At 24 hours of age, generalized seizures were treated

with phenobarbital. On the second day of life, the blood

culture grew group B Streptococcus and the infant was

treated with penicillin. CSF culture was negative. The infant was irritable and both tone and movement were

decreased in the right arm. An EEG on day 3 was normal. A CT scan on day 6 showed a large area of low density in the distribution of the left middle cerebral artery (Fig

4, left). Ultrasound scan of the head at 26 days of age

showed an echodense area in the left parietal region

superior to the Sylvian fissure (Fig 4, right) and in the same position as the area of decreased density noted on CT scan. The left lateral ventricle was dilated slightly,

and there was an increase in pulsations of the arteries

around the echodense area and an absence of pulsations

within the lesion. The remainder of the hospital course

was unremarkable. At the time of discharge on day 28 of life, there was a mild facial weakness, increased tone, and

decreased movement on the right. The deep tendon re-flexes were brisker in the right than the left arm and were symmetrical in the lower extremities.

DISCUSSION

This report deals with the appearance of focal echodense areas on cranial ultrasound scan in the newborn and the correlation of these lesions with the CT appearance of areas of low density, known

to represent ischemic ry5

Fig 4. Left, Computed tomographic scan (age 6 days)

shows area of decreased density in distribution of left

middle cerebral artery. Right, Anterior coronal ultra-sound scan (age 25 days) shows area of increased echoes in left hemisphere (arrow).

Focal ischemic injury in the newborn occurs most

commonly in the distribution of one of the major

cerebral vessels.’ The frequency of occurrence of

such injury was studied by Barmada et al.6 In a

series of 592 autopsies, infarcts were of arterial

origin in 32 (5.4%) and venous origin in 14 (2.4%).

The middle cerebral artery was affected most

fre-quently. In three of the four cases reported here,

infarction was in the distribution of the left middle

cerebral artery.

The most common etiology is thromboembolism,

associated with disseminated intravascular

coagu-lation,6 placental infarcts, involuting fetal

yes-sels,7 8 and traumatized vessels (eg, punctured or

catheterized). Developmental abnormalities of cer-ebral vessels appear to be less common.9 General-ized cerebral hypoperfusion, which may follow per-inatal asphyxia, may cause focal ischemic lesions,

usually involving the middle cerebral artery.’#{176} The

mechanism by which such generalized cerebral

hy-poperfusion may produce focal ischemic lesions is

not fully understood.

In the neonatal period hemiparesis or focal

sei-zures may accompany focal infarction. Thus, in

cases 2 and 4 there was a persistent right

hemipa-resis and in cases 1 and 2 focal seizure activity was

shown on the EEG.

The use of both technetium and CT scanning has

been reported for the diagnosis of focal cerebral

ischemic lesions in the newborn.”0” Thus,

O’Brien et al,’#{176}in a study with technetium scans of 85 asphyxiated term infants, observed increased uptake of radionuclide in a middle cerebral artery

distribution in 20% of patients. With CT scan,

Fitzhardinge et ‘ reported an incidence of middle

cerebral artery involvement in 15% of asphyxiated

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ARTICLES

793

In this report we have described the use of

ultra-sound scanning for the diagnosis of cerebral is-chemic lesions in four infants. The focal areas of increased echodensity seen on ultrasound scan cor-respond to the appearance on CT scan of areas of decreased density which are known to represent ischemic cerebral Furthermore, on

real-time ultrasound scanning in two cases, changes of

arterial pulsations were observed in cerebral vessels

in the area of the lesions. Thus, in both, there was

a diminution in pulsations within the echodense

areas, and in one case, an increase in pulsations

was observed at the periphery of the echodense

lesion.

Although neuropathologic studies were not avail-able to define the lesions absolutely, it appears most probable that the echodense areas observed on ultrasound scans represent ischemic cerebral le-sions. Thus, in case 1, CT scan demonstrated a hypodense region (representing an ischemic rather than hemorrhagic lesion) nine days following the demonstration of an echodense area of ultrasound

scan. Had this echodense area represented a

hem-orrhagic lesion, persistence of blood would be ex-pected on the CT scan only nine days later. In case 2, the EEG on day 3 showed evidence of a focal cerebral lesion in the left hemisphere and the CT

scan on day 6 demonstrated a focal area of low

density, also in the left hemisphere. It seems

un-likely that this focal ischemic lesion, which oc-curred on or before day 3, and which had not become hemorrhagic by day 6, became hemorrhagic

over the subsequent four days prior to ultrasound

scan on day 10. In case 3, CT scan on day 30 did

not demonstrate any evidence of hemorrhage. Again, it seems unlikely that such a lesion (which

most probably occurred during the period of

hyper-tension in the early neonatal period) would become

hemorrhagic between days 30 and 41 of life during which time the infant’s condition was stable.

The explanation of why ischemic cerebral injury appears hyperechoic is unclear. Although the

pos-sibility that such hyperechoic areas represent

edema cannot be excluded, it seems unlikely as edema more commonly appears hypoechoic on ultrasound. An alternative explanation is that,

fol-lowing ischemic injury, there is a decrease in tissue

fluid in these areas resulting in increased echoes on

ultrasound. Clearly, further studies involving

neu-ropathologic correlation are necessary to resolve

this issue.

Our data demonstrate the value of ultrasound scanning for assessment of the extent and location

of focal cerebral ischemic lesions in the newborn.

Because ultrasound scanning is noninvasive and

may be performed simply at the bedside, it is

pos-sible to perform serial scans which may provide

important information concerning the neurologic

correlates and evolution of such ischemic lesions.

REFERENCES

1. Volpe JJ: Neurology of the Newborn. Philadelphia, WB

Saunders, 1981

2. Allan WC, Roveto CA, Sawyer CR, et al: Sector scan ultra-sound imaging through the anterior fontanelle: Its use in

diagnosing neonatal periventricular-intraventricular

hem-orrhage. Am J Dis Child 1980;134:1028

3. Pape KE, Blackwell RJ, Gusick G, et al: Ultrasound

detec-tion of brain damage in preterm infants. Lancet 1979;1:1261 4. Hill A, Melson GL, Clarke HB, et al: Hemorrhagic

periven-tricular leukomalacia: Diagnosis by real-time ultrasound and correlation with autopsy findings. Pediatrics 1982;69:282

5. Flodmark 0, Becker LE, Harwood-Nash DC, et al: Corre-lation between computed tomography and autopsy in pre-mature and full-term neonates that have suffered perinatal asphyxia. Radiology 1980;137:93

6. Barmada MA, Moosy J, Shuman RM: Cerebral infarction with arterial occlusion in neonates. Ann Neurol 1979;6:495

7. Larroche JC: Developmental Pathology of the Neonate. Am-sterdam, Elsevier, North Holland, 1977

8. Friede RL: Developmental Neuropathology. New York, Springer-Verlag, 1975

9. Stewart RM, Williams RS, Kukl P, et al: Ventral porence-phaly: A cerebral defect associated with multiple congenital anomalies. Acta Neuropathol 1978;42:231

10. O’Brien MJ, Ash JM, Gilday DL: Radionuclide brain scan-fling in perinatal hypoxia-ischemia. Dev Med Child Neurol

1979;21:161

11. Fitzhardinge PM, Fitz CR, Harwood-Nash DC: Follow-up studies of infants with abnormal neonatal computed torn-ography (CT) resulting from asphyxia. Pediatr Res 1978;12:551

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1983;71;790

Pediatrics

Alan Hill, David J. Martin, Alan Daneman and Charles R. Fitz

Correlation with Computed Tomographic Scan