Clinical Brief

Intracranial Arteriovenous Malformation with Maternal
Carbamazepine Use
Manish Narang, Dheeraj Shah and Gupta Natasha1
Department of Pediatrics, University College of Medical Sciences and GTB Hospital, Delhi, 1Department of
Radiology, Aruna Asif Ali Government Hospital, Delhi

ABSTRACT
1½ month old child born to primigravida mother on prolonged carbamazepine therapy presented with recurrent seizures. The
child had abnormal facies and was diagnosed to be having arteriovenous malformation with intracranial hemorrhage on
neuroimaging. This case suggests that development of arteriovenous malformation in a child with maternal carbamazepine
therapy may occur as a part of clinical profile of ‘fetal anticonvulsant syndrome’. [Indian J Pediatr 2007; 74 (1) : 85-86]
E-mail: manish_2710@yahoo.com

Key words : Intracranial arteriovenous malformations; Maternal carbamazepine therapy; Fetal anticonvulsant syndrome

Arteriovenous malformations (AVM) are thought to be
congenital lesions that derive from the failure of normal
maturation of primitive vascular networks during
embryogenesis. Here it is reported the association of a
cerebral arteriovenous malformation in an infant with the
maternal use of carbamazepine.
CASE REPORT
A 1½-month-old child was brought to emergency room
with history of mild intermittent fever for 2 days and
multiple episodes of left focal convulsions in the last 12
hours. Child was born to 24-year-old primigravida at
term, cried soon after birth and was on exclusive breast
feeds. Mother was known epileptic and was on
carbamazepine (900 mg daily) for last 9 years. The
seizures were well controlled except at 6 month of
gestation when the dose had to be hiked to 1200 mg daily.
The child weighed 3.75 Kg and had occipitofrontal
circumference of 38 cm. Abnormal facial features present
in the child were hypertelorism, midface hypoplasia and
micrognathia. He also had feeble cry and poor activity.
Anterior fontanelle was not bulging. Tone was increased
with brisk deep tendon reflexes and ill-sustained ankle
clonus. Possible diagnosis of hypocalcemic convulsion
was kept and child was started on intravenous calcium

gluconate but child continued to have left focal
convulsions. Lumbar puncture done on admission
revealed hemorrhagic cerebrospinal fluid (CSF) and was
presumed to be traumatic. Repeat lumbar puncture done
on day-3 of admission revealed xanthochromic CSF
having plenty of RBCs with protein of 128 mg/dL and
sugar of 58 mg/dL.
On day-4 of admission child developed excessive cry
followed by apneic episodes. In view of hemorrhagic CSF
and a deteriorating child, diagnosis of intracranial bleed
was suspected. Ultrasonography of skull was done which
showed right parietal cystic space occupying lesion. Child
developed several episodes of left focal convulsions on
day-6 and was started on phenobarbitone. On careful
auscultation, bruit was heard on anterior fontanelle. CT
scan (brain) suggested the presence of an AV
malformation in right fronto-parietal region and
surrounding hemorrhage with intraventricular extension.
MRI brain was suggestive of a large AV malformation
with nidus in right high fronto-parietal region. The
malformation had a feeding vessel from right middle
cerebral artery and drainage to superior sagittal sinus
(Fig.1). There was also a subacute hematoma in right
fronto-temporal lobe with mass effect and midline shift
with obstructive hydrocephalus and intraventricular
hemorrhage.
Child was managed conservatively and was referred
for neurosurgical intervention when stabilized. The baby
was operated for AV malformation elsewhere but died
later as reported by parents in follow up.

Correspondence and Reprint requests : Dr. Manish Narang, A 16/
F1, Dilshad Garden, Delhi- 110095.

Indian Journal of Pediatrics, Volume 74—January, 2007

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Manish Narang et al

Fig. 1. T2 weighted MR image of the brain showing a large
serpigenous lesion suggestive of AVM in the right
frontoparietal region fed by middle cerebral artery
surrounded by large area of parenchymal bleed in various
stages.

DISCUSSION
Proper seizure control with appropriate anticonvulsant
therapy is the primary goal in treating women with
epilepsy. 1 The commonly used anticonvulsants are
established human teratogens.2 Congenital malformations
were more common among offspring of women on
antiepileptic medications (4.6%) than among offspring of
untreated patients (2.8%).3 The neonate born to mothers
on anticonvulsant therapy should therefore be assessed
carefully for epilepsy and anticonvulsant associated
dysmorphology.
In the present case, the mother took anticonvulsant
therapy for 8 years which continued throughout
conception. This baby had abnormality of facial features
consistent with fetal carbamazepine teratogenecity. 4
Maternal carbamazepine has been shown to be associated
with fetal cardiac malformations like atrial septal defect,
transposition of great arteries and ventricular septal
defect. 5 The association of carbamazepine with
arteriovenous malformations has not been reported in
literature to the best of author's knowledge. However, as
carbamazepine is known to be associated with
cardiovascular teratogenecity, it is possible that
arteriovenous malformation in the present case was due
to carbamazepine therapy.
AVMs are considered congenital lesions and are

86

characterized by failure of the embryonic vascular plexus
to fully differentiate and develop a mature capillary bed
in the affected area. AV malformations are typically
located in cerebral hemispheres, but may be situated in
cerebellum, brain stem or spinal cord.6 The formation of
AVMs probably relates to sequential formation and
resorption of cerebral surface veins. Their structure may
change and grow postnatally but only in relation to a
prenatally existing lesion. Molecular biologic factors are
thought to be important to AVM development. These
may include vascular endothelial growth factor (VEGF)
and basic fibroblast growth factor (bFGF). Anticonvulsant
induced teratogenecity has been suggested to be due to
inhibition of enzyme epoxide hydrolase resulting in
accumulation of teratogenic epoxide intermediates of
antiepileptic drugs. 7 Perinatal events disrupting
angiogenesis thus have a potential to cause arteriovenous
malformations.
The author's believe that the development of AV
malformation in the child of mother with carbamazepine
therapy during pregnancy represents a possible etiology
and adds to the clinical profile of “fetal anticonvulsant
syndrome”. Considering the fact that cardiovascular
malformations can be successfully tackled surgically; it
may be worthwhile screening babies of mothers with long
term anticonvulsant therapy for any cardiovascular
malformation including AVM. Since this is a surgical
emergency, the need for early diagnosis cannot be
overemphasized.
REFERENCES
1. Crawford P. Best practice guidelines for the management of
women with epilepsy. Epilepsia 2005; 46 (Suppl 9) : 117-124.
2. Yerby MS, Leavitt A, EricKson B, McComick KB, Loewenson
RB, Sells CJ et al. Antiepileptic drugs and the development of
congenital anomalies. Neurology 1992; 42 : 132-140.
3. Artama M, Auvineu A, Raudaskoski T, Isojarvi I, Isojarvi J.
Antiepileptic drug use of women with epilepsy and congenital
malformations in offspring. Neurology 2005; 64 : 1874-1878.
4. Jones KL, Lacro RV, Johnson KA, Adams J. Pattern of
malformations in the children of women treated with
carbamazepine during pregnancy. N Engl J Med 1989; 320:
1661-1666.
5. Gupta G, Bansal A, Singh M. Antenatal Carbamazepine use
associated with d-TGA and ASD. Indian Pediatr 2002; 39: 101102.
6. Halem RHA. The nervous system: Intracerebral hemorrhage.
In Behrman, Kliegman, Jenson, eds. Nelson Textbook of
Pediatrics. Philadelphia; WB Saunders Co; 1999; 1856.
7. Lindhout D, Hoppener RJ, Meinardi H. Teratogenicity of
antiepileptic drug combinations with special emphasis on
epoxidation (of carbamazepine). Epilepsia 1984; 25 : 77-83.

Indian Journal of Pediatrics, Volume 74—January, 2007