Pediatrics International (2008) 50, 696–697

doi: 10.1111/j.1442-200X.2008.02715.x

Patient Report

Congenital cystic periventricular leukomalacia in a
small-for-gestational age full-term infant
Akihisa Nitta, Hiroshi Suzumura, Kenichi Kano and Osamu Arisaka
Department of Pediatrics, Dokkyo Medical University, School of Medicine, Mibu, Tochigi, Japan
Key words

cystic periventricular leukomalacia, full-term, small-for-gestational age, ventricular dilatation, West syndrome.

The mother was 36 years old with a birth history of gravida two
para 2. Fetal ultrasonography indicated mild ventriculomegaly
from 22 weeks of gestation and intrauterine growth retardation
from 28 weeks of gestation (Fig. 1), with unexplained causes.
The mother had gestational diabetes, which was being monitored
without medication, and pre-natal infections including toxoplasma, rubella, herpes and cytomegalovirus infection during
pregnancy, but these were ruled out as causes.

After discharge from the neonatal intensive care unit the
patient had a generalized spasm at 2 months of age. EEG showed
a spike and wave complex in the left hemisphere. At 4 months
of age the patient had a tonic spasm and an EEG showed hypsarrhythmia. Brain MRI at 6 months of age showed irregular
ventricular dilatation and loss of white matter (Fig. 3). Thus, we
diagnosed West syndrome and subsequently the patient developed
spastic quadriplegia.

Case report

Discussion

A small-for-gestational age (SGA) infant was born at 40 weeks
of gestation, with birthweight 1806 g; height 44 cm, and head
circumference 30.7 cm. Apgar scores were 9 and 10 at 1 and
5 min, respectively, and no abnormal pathological findings were
found in the placenta and umbilical cord. The infant appeared
alert and looked healthy without spasms. Primitive reflexes
including palmar grasp, rooting, and a Moro reflex were present,
and no hypotonia and spasticity were noted on physical examination. Laboratory data at birth were pH 7.402, PCO2 33.7 mmHg,
HCO3 20.9 mmHg, white blood cells 11 600/␮L, hemoglobin
18.5g/dL, platelet count 163 000/␮L, aspartate aminotransferase
32 IU/L, alanine aminotransferase 3 IU/L, total/direct bilirubin
2.7/0.5 mg/dL, lactate dehydrogenase 970 IU/L, blood urea
nitrogen 10 mg/dL, creatinine 0.8 mg/dL, glucose 62 mg/dL,
Na 141 mEq/L, K 5.0 mEq/L, Cl 105 mEq/L, Ca 9.6 mg/dL,
C-reactive protein <0.01 mg/dL, IgM 8 mg/dL and karyotypic
analysis 46, XY.
Brain computed tomography (CT) at birth showed irregular
ventricular dilatation and cystic periventricular leukomalacia (PVL)
near the left ventricular anterior horn (Fig. 2a), and brain ultrasonography (US) showed the same findings. Brain magnetic resonance imaging (MRI) at 7 days of age showed cystic PVL and
irregular ventricular dilatation (Fig. 2b,c). Auditory brainstem
response audiometry at 13 days of age showed no abnormal findings, and an electroencephalogram (EEG) at 14 days of age
showed slightly low activity but no epileptic waves.

In this report we describe an SGA full-term infant with cystic
PVL at birth. Although cystic PVL in premature infants is the
major neuropathology for spastic motor deficits in cerebral palsy
or epilepsy,1 cystic PVL in full-term infants is a rare neurological
disorder of which the characteristics remain unknown.
Most cases of PVL in full-term infants are diagnosed after
4 months of age based on clinical manifestations, including
developmental delay, motor abnormalities, and a history of seizures. Miller et al. described 12 full-term children with PVL,
including seven with PVL of unexplained cause at 24.4 months.2
These cases, however, did not include cystic PVL. Sie et al. also
reported PVL in 19 full-term infants, and found that the most
commonly encountered risk factors were dysmaturity or maternal
pre-eclampsia during pregnancy;3 but once again there were no
cases of cystic PVL.
The characteristics of occurrence of cystic PVL in an SGA
infant are poorly understood. Ancel et al. suggested that the risk
of cystic PVL may be lower among preterm SGA infants born to
mothers with hypertension, antenatal hemorrhage, or preterm
premature rupture of the membrane, compared to infants born
after preterm premature rupture of the membrane with short
latency and idiopathic preterm labor.4
Murata et al. described early changes associated with cystic
PVL that may be apparent histologically within hours of insult, but
at least 2–6 weeks are required before lesions can be visualized on
US.1 Therefore, if cystic PVL is observed within 7 days after birth,
the origins must be intrauterine,1 and we suggest that the cause of
cystic PVL in fetal onset is different from that in postnatal onset,
based on the reports of Yamamoto et al.5 and Nakamura et al.6
Yamamoto et al. investigated the fetal brain on transvaginal US
and examined the relationship between fetal periventricular echodensity (PVE) and neonatal PVL. In PVE the quantified echogenicity

Correspondence: Akihisa Nitta, MD, Department of Pediatrics,
Dokkyo Medical University, School of Medicine, Kitakobayashi 880,
Mibu, Shimotsuga-gun, Tochigi, 321-0293, Japan. Email: a-nitta@
dokkyomed.ac.jp
Received 19 November 2005; revised 17 August 2006; accepted
17 January 2007.

© 2008 Japan Pediatric Society

Cystic periventricular leukomalacia

Fig. 1 Fetal ultrasonography at 30 weeks of gestation, showing mild
ventriculomegaly.

is higher than in a normal brain, and PVE usually precedes the
occurrence of PVL. No cystic PVL was found in US of the fetal
brain in 63 high-risk fetuses at 17–32 weeks of pregnancy; instead,
fetal PVE was detected in 42 fetuses, and the authors concluded that
neonatal PVL was preceded by antenatal persistent fetal PVE.5
Nakamura et al. reported two autopsy cases of cystic brain
lesions in utero. The first infant was born at 27 weeks of gestation
with a birthweight of 460 g as a donor in twin-to-twin transfusion
syndrome, and died immediately after birth. An autopsy showed
multicystic encephalomalacia in the distribution of the anterior
cerebral artery. The second infant was stillborn at 30 weeks of

697

Fig. 3 Brain magnetic resonance image at 6 months of age showing
irregular ventricular dilatation and loss of white matter.

gestation at a birthweight of 1030 g. An autopsy showed thanatophoric dysplasia with associated chronic PVL. The authors concluded that multicystic encephalomalacia and chronic PVL were
caused by persistent circulatory disturbance in utero.6
In the present patient, although mild fetal ventriculomegaly
was noted from 22 weeks of gestation, PVE and cystic PVL were
not observed during pregnancy. We speculate that some persistent circulatory disturbance, perhaps induced by a traumatic
event, may have occurred before 22 weeks of gestation and fetal
PVE may have developed at that time, but we were unable to
obtain information about traumatic events that may have affected
the mother. We were also unable to perform fetal MRI, which
would have been helpful for diagnosis of antenatal cystic PVL.
Consequently, we propose that a diagnosis of congenital cystic
PVL is appropriate for the patient, and our experience suggests
that congenital cystic PVL in full-term SGA infants should be
considered as a possible diagnosis in cases where fetal ventriculomegaly is noted on antenatal examination.

References

Fig. 2 (a) Computed tomography scan at birth, showing cystic periventricular leukomalacia (PVL) and ventricular dilatation. (b) Diffusion
magnetic resonance image at 7 days of age, showing cystic PVL
and irregular ventricular dilatation. (c) T1-weighted MR image at 7 days
of age, showing cystic PVL and irregular ventricular dilatation.

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Possible antenatal and perinatal related factors in development of
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2 Miller SP, Shevell MI, Patenaude Y, O’Gorman AM. Neuromotor
spectrum of periventricular leukomalacia in children born at term.
Pediatr. Neurol. 2000; 23: 155–9.
3 Sie LT, van der Knaap MS, Oosting J, de Vries LS, Lafeber HN, Valk
J. MR patterns of hypoxic-ischemic brain damage after prenatal,
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4 Ancel PY, Marret S, Larroque B et al. The Epipage Study Group.
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J. Obstet. Gynecol. 2005; 193: 178–84.
5 Yamamoto N, Utsu M, Serizawa M et al. Neonatal periventricular
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6 Nakamura Y, Fujiyoshi Y, Fukuda S et al. Cystic brain lesion in
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© 2008 Japan Pediatric Society