Clinical Brief

Status Epilepticus and Capillary Leak Syndrome in a
Neonate Related to Perinatal Hypoxic-ischemic
Encephalopathy
Belma Saygili Karagol, Omer Erdeve, Saadet Arsan, Begum Atasay, Mesiha Ekim1, Serap Teber2 and
Gulhis Deda2
Division of Neonatology, 1Division of Pediatric Nephrology, and 2Division of Pediatric Neurology, Department of
Pediatrics, Ankara University School of Medicine, Ankara, Turkey

ABSTRACT
Hypoxic-ischemic cerebral injury that occurs during the perinatal period is one of the most commonly recognized cause of
long-term neurological deficit in children, often referred to as cerebral palsy. We describe a case with capillary leak
syndrome and seizures to co-morbid status epilepticus related to perinatal hypoxicischemic encephalopathy in newborn
period. [Indian J Pediatr 2010; 77 (4) : 439-441] E-mail: belmakaragol@ yahoo.com

Key words: Hypoxic-ischemic cerebral injury; Capillary leak syndrome; Status epilepticus; Inflammatory mediators

[Received June 16, 2009; Accepted October 19, 2009]

neonate was bradycardic and Apgar scores were 2 and
7 in 1 and 5 min respectively. Seizures developed 6 hrs
after birth and did not respond to intravenous
diazepam, so that the patient was transferred to the
neonatal intensive care unit (NICU). On admission at
our NICU, he was lethargic with generalized muscle
rigidity and physical examination revealed cephal
hematoma with 4x4 cm. Deep tendon reflexes were
hyperactive and plantar reflexes were flexor. An
electroencephalogram (EEG) on the day of admission
was markedly abnormal, with low-voltage and
disorganized background activity. A cranial computed
tomography (CT) scan demonstrated manifest cephal
hematoma but no brain edema or hemorrhage. On day
3, neurological symptoms of severe asphyxia presented
with generalized clonic seizures. Antiepileptic therapy
with phenytoin was started as initial therapy. On the
following days, phenobarbital, midazolam and lidocain
were additionally required in order to control seizures
expressed as status epilepticus. A repeat CT scan on
10th day showed generalized ischemia with
hypodansity in all areas. Brain magnetic resonance
imaging on day 13 showed abnormally high signal
intensity in the cortical areas involving the basal
ganglia and thalamus on T1 weighted images
secondary to asphyxia (Fig. 1). On day 14, severe
generalized edema appeared (Fig. 2A). His actual
weight was 4670g. Capillary leakage syndrome with
generalized edema and decrease of plasma protein
concentrations (serum albumin level: 2.2 g/dL) existed.
Prerenal insufficiency due to fluid restriction with blood

Indian Journal of Pediatrics, Volume 77—April, 2010

439

Hypoxic-ischemic cerebral injury that occurs during the
perinatal period is one of the most commonly
recognized cause of long-term neurological deficit in
children, often referred to as cerebral palsy.1 Expression
of inflammatory mediators has been demonstrated in
the pathogenesis of hypoxic-ischemic brain injury. 2
Inflammatory cytokines also appear to exert in capillary
leak syndrome, which may progress to end organ
dysfunction and result in death by extravascular fluid
accumulation with severe edema.3 We describe a case
with capillary leak syndrome and seizures to co-morbid
status epilepticus related to perinatal hypoxic- ischemic
encephalopathy in newborn period.
REPORT OF CASE
A male infant was born by vaginal delivery at 40 wks
gestation to a 23-yr-old primigravida woman after an
uneventful pregnancy. The mother was brought to the
hospital after the contractions had started, and the
child was delivered by using vacuum extraction
because of prolonged labour and fetal distress. The

Correspondence and Reprint requests : Dr Belma Saygili
Karagol, Mesa Koru sitesi Mimoza A Blok No: 14 06830
Çayyolu/Ankara Turkey.
[DOI-10.1007/s12098-010-0011-7]

Belma Saygili Karagol et al

A

B

Fig. 1. Magnetic resonance imaging revealed abnormally high
signal intensity in the cortical areas involving the basal
ganglia and thalamus on T1 weighted images secondary
to asphyxia.

urea nitrogen as 69 mg/dL, creatinin 0.67 mg/dL and
normal serum sodium level (Na: 143 mEq/L)
accompanied capillary leak. There was not any positive
clinical and hematological septic score. Liver function
tests were also normal. Generalized severe edema
increased within following three days and
concentrations of inflammatory mediators as TNF-a, IL6, and IL-8 were reported as 14.3, 3.2 and 63.4 pg/mL
respectively. Methylprednisolon therapy with 2 mg/
kg/day dose was started intravenously on day 17. On
the same day, the antiepileptic drug regimen was
changed into monodrug treatment with valproate and
all other drugs were ceased because of intractable
seizures that could have not been controlled with the
drugs. After the initiation of methylprednisolon
treatment, generalized edema decreased day by day and
the patient became stable with monodrug antiepileptic
treatment on the 22nd day (Fig. 2B). TNF-a, IL-6 and IL8 concentrations decreased to 3.6, 1.2 and 8.7 pg/mL
respectively after the corticosteroid use. The patient was
discharged from hospital with full oral feeding and oral
valproate treatment on the 26th day.
On follow up examination at 3 month of age, he had
not experienced any seizure activity during his home
stay. On physical examination, he expressed truncal
hypotonicity and exhibited mild rigidity of the lower
extremities. Eye movements were normal and there was
no muscle weakness or fasciculation in extremities. The
response to sound stimuli was normal.
440

Fig. 2. (A) Capillary leakage syndrome with generalized odema
manifested in the patient on 14th day. (B) Physical
appearence of the patient changed almost to normal after
generalized odema disappeared.

DISCUSSION
The existence of capillary leak syndrome and status
epilepticus related to perinatal hypoxic-ischemic
encephalopathy in our patient prompted us to consider
relationship between brain injury and expression of
inflammatory mediators. Cardiopulmonary bypass and
sepsis related capillary leak syndrome in pediatric
patients have been previously reported.3-5 Nevertheless,
hypoxic-ischemic encephalopathy related capillary
leak syndrome has not been described in literature in
newborns. Our patient with capillary leak syndrome
had significantly decreased plasma protein
concentrations and developed generalised edema,
which were the criteria used to define the syndrome in
other studies. 3-6 All other ethiologies of edema were
excluded.
IL-6, IL-8 and TNF-a are important inflammatory
mediators and have been reported to increase capillary
permeability.5-9 Inflammatory cytokines appear to exert
both beneficial and deleterious effects following
ischemia. This dual effect may complicate the task of
developing hypoxic-ischemic brain injury and capillary
leakage against the inflammatory response. Activation
of these cytokines in our patient were also supportive
clues for capillary leak syndrome determination.
However, data reported on the inflammatory response
induced by these concentrations of inflammatory
mediators is not sufficient. Additionally, there aren’t
defined normal ranges of these cytokins belonging to
the neonatal period. Elevated concentrations of these
Indian Journal of Pediatrics, Volume 77—April, 2010

Status Epilepticus and Capillary Leak Syndrome Related to Perinatal Hypoxic-ischemic Encephalopathy
inflammatory mediators on the 14th day and decreased
concentrations on the 22nd day might be a clue for
diagnostic approach to capillary leak syndrome in our
patient.
Suzuki et al reported the high incidence of cytokinerelated disease as the cause of death in children with
perinatal hypoxic-ischemic encephalopathy sequelae.
They also emphasized that the pathogenesis of this
disease needed to be clarified. 10 However, they
concluded that cytokine-related disease with perinatal
hypoxic-ischemic encephalopathy sequelae occur in
childhood period whereas our patient suffered from
capillary leak syndrome and status epilepticus in the
neonatal period. Furthermore, limited data about the
time of release and activation of inflammatory mediators
from cells in hypoxia ischemia are available. Hagberg et
al reported that expression of inflammatory mediators
in the pathogenesis of hypoxicischemic brain injury has
been demostrated within 1-4 hour following hypoxia
ischemia in neonatal rats.2
Inflammatory mediators seem to play a critical role in
the pathogenesis of hypoxicischemic brain injury. 2
Various patterns of hypoxic encephalopathy occur in
asphyxiated neonates.1 We conclude that inflammatory
mediators may play a role in the development of the
present case clinic situation. However, understanding
the pathogenesis of perinatal hypoxia may clarify the
relationship between capillary leak syndrome and
hypoxic-ischemic cerebral injury in future.
Contributions: The manuscript has been written and prepared by
BSK; OE and SA have revised the manuscript; BA has attended
the progress of this case together with all other authors in NICU.
The patient has been consulted for pediatric Nephrology by ME.
The patient has been also consulted for pediatric Neurology for
drug choice by ST and GD.
The case was carried out in the NICU. All authors followed the
case in NICU.

Indian Journal of Pediatrics, Volume 77—April, 2010

Conflict of Interest: None.
Role of Funding Source: None.

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