Surgical treatment of a neonate with refractory seizures secondary to congenital giant cell astrocytoma: case report and literature review.

Abstract

Congenital brain tumours are rare. They account for 0.5% to 1.9% of intracranial tumours in childhood and have an incidence of 0.34 per million live births. Most congenital brain tumours are neuro-ectodermal tumours and medulloblastomas; giant cell astrocytoma and other tuberous sclerosis-related tumours are rare. We report on a neonate who developed seizures that were refractory to medical treatment. Imaging studies revealed a right frontal calcified tumour. Surgical resection was performed successfully and pathology revealed the tumour to be a giant cell astrocytoma. The child was seizure-free afterwards.

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222 Hong Kong Med J Vol 12 No 3 June 2006
CASE REPORT
Surgical treatment of a neonate with
refractory seizures secondary to
congenital giant cell astrocytoma:
case report and literature review
Key words:
Astrocytoma;
Infant, newborn;
Seizures;
Tuberous sclerosis
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The Chinese University of Hong Kong,
Prince of Wales Hospital, Shatin, Hong
Kong:
Division of Neurosurgery
SF Hon, MB, ChB
GKC Wong, FRCS (Edin)
XL Zhu, FRCS (Edin)
WS Poon, FRCS (Glasg)
Department of Anatomical and Cellular
Pathology
HK Ng, FRCPath
Department of Paediatrics
NC Sin, MRCPaed
Correspondence to: Prof WS Poon
(e-mail: wpoon@surgery.cuhk.edu.hk)
SF Hon ??
GKC Wong ??
XL Zhu ??
HK Ng ??
NC Sin ??
WS Poon ??
Congenital brain tumours are rare. They account for 0.5% to 1.9% of
intracranial tumours in childhood and have an incidence of 0.34 per million
live births. Most congenital brain tumours are neuro-ectodermal tumours
and medulloblastomas; giant cell astrocytoma and other tuberous
sclerosis–related tumours are rare. We report on a neonate who developed
seizures that were refractory to medical treatment. Imaging studies revealed
a right frontal calcified tumour. Surgical resection was performed success-
fully and pathology revealed the tumour to be a giant cell astrocytoma. The
child was seizure-free afterwards.
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Introduction
Giant cell astrocytoma is a benign tumour and one of the primary features of
tuberous sclerosis. Neonatal presentation is rare. We report the management of a
neonate with seizures that commenced on day 1 after birth and were refractory to
medical treatment.
Case report
The female neonate was delivered at full term by Caesarian section under spinal
anaesthesia in October 2002. She was the second child of the family and weighed
2.65 kg. There was no maternal history of drugs, smoking, alcohol, or teratogenic
exposure. No dysmorphic features or dermatological stigmata were found. The
patient developed the first seizure 6 hours after delivery. Most seizures began
with bilateral clonic movements of the upper limbs that spread to involve the
lower limbs. They were difficult to categorise but were generalised seizures.
They occurred daily in the first 5 weeks of life and developed into status
epilepticus at 5 weeks of age. Urgent computed tomographic brain imaging on
day 1 after birth revealed a wedge-shaped right fronto-parietal hyperdense lesion
without mass effect or perifocal oedema and with normal ventricles (Fig 1a).
Magnetic resonance imaging (MRI) of the brain on day 3 showed a T1
hyperintense lesion, and T2 hypointense lesion at the same region with no
significant enhancement, and negative for haemosiderin (Fig 1b). An electroen-
cephalogram demonstrated epileptic discharges over the corresponding area (Fig
2a). A tumour mass with calcification foci was suspected. She was anaesthetised
with intravenous thiopentone (7 mg/kg per day) at 5 weeks of age when she
developed status epilepticus. Seizures had previously been unsuccessfully

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Hong Kong Med J Vol 12 No 3 June 2006 223
Neonate with refractory seizure
managed with phenobarbitone 7 mg/kg per day and
carbamazepine 17 mg/kg per day. The electroencephalo-
gram showed a burst suppression pattern with occasional
seizures, although there were no further clinical seizures.
In view of the intractable nature of the seizures despite
maximal antiepileptic medication, and the difficulty of
diagnosis, elective surgery was performed at 6 weeks of
age for seizure control and pathological diagnosis. Her
condition on thiopentone was stable. She was intubated
and ventilated, and treated empirically for sepsis. There
was no evidence of pneumonia. A right fronto-parietal
craniotomy was performed and the area of the lesion was
located by ultrasound. Epileptic activity was recorded
over and around the lesion using strip electrode
electrocorticography (ECoG). The tumour-associated gyrus
and peri-lesional tissue were excised under ECoG guidance.
The excision margin was grossly clear. The pathological
diagnosis was a right frontal giant cell astrocytoma.
(a)(b)
Fig 1. (a) Plain computed tomogram showing right frontal hyperintensity (arrow); and (b) magnetic resonance image showing
non-enhancing right frontal lesion and with no evidence of haemorrhage (arrow)
(a)(b)
Fig 2. (a) Ictal electroencephalogram and (b) section of tumour showing numerous large astrocytes, occasionally binucleated,
with glassy eosinophilic cytoplasm and coarse fibres; dystrophic calcification was seen in the neuropil (H&E, x 150)

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Hon et al
224 Hong Kong Med J Vol 12 No 3 June 2006
Microscopic examination revealed that the tumour had
apparently arisen from large clusters of highly dysplastic
cells in the cortex. The tumour was not a subependymal
giant cell astrocytoma (SGCA) and not considered
tuberous sclerosis–related since it was close to the ventricle
but did not protrude into the lumen. The World Health
Organization grading was grade I (Fig 2b).
Her postoperative recovery was uneventful. One episode
of seizure was detected on day 15 postoperatively but none
thereafter. She continued receiving maintenance doses of
lamotrigine, tegretol, and phenobarbitone. A postoperative
MRI of the brain showed no residual or recurrent tumour
with global cerebral atrophy. She was discharged from
hospital 2 months after surgery and referred for special
training and assessment. She was nearly 3 years of age
(2 years 11 months) at the last follow-up and weighed
10 kg. Maintenance therapy consisted of lamotrigine 10 mg
every morning and 15 mg at night. She had experienced
only one breakthrough seizure in the prior 6 months. She
had spastic tetraparesis. She could turn but was unable to
sit unsupported. She could make verbal responses but
demonstrated no visual fixation. Marked visual impairment
was suspected.
Discussion
Congenital brain tumours are rare. They account for 0.5%
to 1.9% of intracranial tumours in childhood with an
incidence of 0.34 per million live births.1 The majority of
such tumours are neuro-ectodermal tumours and
medulloblastomas; giant cell astrocytoma or other tuberous
sclerosis–related tumours are rare. Maternal exposure to
teratogens during gestation (such as radiation and drugs) is
a major risk factor for congenital brain tumours. In more
than half of all cases, the clinical presentation consists of
macrocephaly and symptoms/signs of raised intracranial
pressure such as bulging fontanelles. Subependymal giant
cell astrocytomas account for 1.5% of paediatric brain
tumours.2 The first two cases of SGCA were reported in
1984 and only 10 cases of neonatal SGCA have since been
reported.3-5 Systematic epidemiological review is thus not
possible. Tuberous sclerosis is usually diagnosed in late
childhood when most of the cutaneous diagnostic criteria
have become evident.6
The typical findings of giant cell astrocytoma in
tuberous sclerosis on MRI are hypointensity on the T1-
weighted image and hyperintensity on the T2-weighted
image with contrast enhancement. The lesion usually lies
adjacent to the foramen of Monro with heterogeneous
calcification and causes obstruction. However, in neonates
the findings may be atypical with hyperintensity on the T1
image and hypointensity on the T2 image. Stricker et al7
suggested that this was due to the higher water concentra-
tion in the immature brain, hypercellularity of the tumour,
and calcification. The case presented here differed in the
tumour location and the lack of mass effect and preserved
ventricles.
Surgery on neonates with brain tumours is a high-risk
procedure due to the danger of profuse bleeding from
vascular tumours. Patients rarely survive the perioperative
period. In five neonates with giant cell astrocytomas who
were treated surgically, only two survived and seizures
persisted.2,4,5,8 Global developmental delay may be part of
the disease nature of tuberous sclerosis. Nonetheless
hypoxic brain damage as a result of recurrent seizures may
also have a significant impact.
Surgical excision has been proposed to offer the best
seizure control in patients with single tubers.4,9,10 In a re-
view of 105 patients with tuberous sclerosis, Cuccia et al11
concluded that seizure and mental retardation could be
improved after surgery without significant morbidity. More
aggressive and early surgery promoted a long seizure-free
survival. Developmental delay was likely to be due to
repeated seizures and, later, status epilepticus.
In general, surgery for neonatal brain tumours
should be deferred until after the neonatal period to
reduce surgical risk. However, in cases such as this one,
where seizure control is not possible, earlier surgery is
indicated. A much better functional outcome might have
resulted.
References
1.Cavalheiro S, Moron AF, Hisaba W, Dastoli P, Silva NS. Fetal brain
tumors. Childs Nerv Syst 2003;19:529-36.
Shepherd CW, Scheithauer BW, Gomez MR, Altermatt HJ, Katzmann
JA. Subependymal giant cell astrocytoma: a clinical, pathological, and
flow cytometric study. Neurosurgery 1991;28:864-8.
Oikawas S, Sakamoto K, Kobayashi N. A neonatal huge subependymal
giant cell astrocytoma: case report. Neurosurgery 1994;35:748-50.
Palmini A, Andermann F, Olivier A, et al. Focal neuronal migration
disorders and intractable partial epilepsy: a study of 30 patients. Ann
Neurol 1991;30:741-9.
Ramenghi LA, Verrotti A, Domzio S, Di Rocco C, Morgese G, Sabatino
G. Neonatal diagnosis of tuberous sclerosis. Childs Nerv Syst 1996;
12:121-3.
Boesel CP, Paulson GW, Kosnik EJ, Earle KM. Brain hamartomas
and tumors associated with tuberous sclerosis. Neurosurgery 1979;
4:410-7.
Stricker T, Zuerrer M, Martin E, Boesch C. MRI of two infants
with tuberous sclerosis. Neuroradiology 1991;33:175-7.
Medhkour A, Traul D, Husain M. Neonatal subependymal giant
cell astrocytoma. Paediatr Neurosurg 2002;36:271-4.
Avellino AM, Berger MS, Rostomily RC, Shaw CM, Ojemann GA.
Surgical management and seizure outcome in patients with tuberous
sclerosis. J Neurosurg 1997;87:391-6.
10. Guerreiro MM, Andermann F, Andermann E, et al. Surgical treatment
of epilepsy in tuberous sclerosis: strategies and results in 18 patients.
Neurology 1998;51:1263-9.
11. Cuccia V, Zuccaro G, Sosa F, Monges J, Lubienieky F, Taratuto
AL. Subependymal giant cell astrocytoma in children with tuberous
sclerosis. Childs Nerv Syst 2003;19:232-43.
2.
3.
4.
5.
6.
7.
8.
9.