Rupture of Middle Cerebral
Artery Aneurysm in a Neonate
CASE REPORT AND REVIEW OF
THE LITERATURE
Falah Maroun, M.D.,* Keyna Squarey, M.D.,* Jacob Jacob, M.D.,* Gerald Murray, M.D.,*
Benvon Cramer, M.D.,* Jane Barron, M.D.,* and Bryce Weir, M.D.**
*Departments of Neurosurgery, Neurology, Pathology and Radiology, Health Sciences
Centre, St. John’s, NF, Canada; and **Section of Neurosurgery, University of Chicago,
Chicago, Illinois.

Maroun F, Squarey K, Jacob J, Murray G, Cramer B, Barron J,
Weir B. Rupture of middle cerebral artery aneurysm in a neonate:
case report and review of the literature. Surg Neurol 2003;59:
114 –9.

ature and describe a ruptured aneurysm of the distal middle cerebral artery (MCA) in a neonate.

BACKGROUND

Intracranial hemorrhage because of rupture of a cerebral
aneurysm is extremely rare in the neonatal period. Delayed diagnosis contributes to high mortality and
morbidity.
CASE DESCRIPTION

The authors report an extremely rare case of a middle
cerebral artery aneurysm diagnosed and treated shortly
after birth. Extensive review of the literature is presented.
The patient died 4 years after surgery. © 2003 Elsevier
Science Inc.
KEY WORDS

Cerebral aneurysm, neonate.

ntracranial arterial aneurysms in the pediatric
age group are rare, comprising 0.5 to 4.6% of all
aneurysms [26]. They are extremely uncommon in
early childhood [3], and even more infrequent in
the neonatal period [3,10]. Morbidity and mortality
are high because of delayed diagnosis and
treatment.
In addition to clinical relevance, the study of cerebral aneurysms identified in early childhood may
help our understanding of pathogenesis of cerebral
aneurysms in all age groups, as the etiopathogenesis of these lesions remains unclear.
Defining the neonatal period as the first 4 weeks
of postnatal life, we identified 14 cases of intracranial aneurysm in the literature. We review the liter-

I

Address reprint requests to: F.B. Maroun, Room 5202, Health Sciences
Centre, 300 Prince Philip Drive, St. John’s, NF, Canada, A1B 3V6
Received December 3, 2001; accepted October 3, 2002.
0090-3019/03/$–see front matter
doi:10.1016/S0090-3019(02)00984-9

Case Report
A 3-day-old newborn male presented with repeated
bouts of focal seizures of the right face, arm, and
leg. He was born spontaneously, at term (birth
weight 3030 g) after an uneventful gestation. The
second stage of delivery was short, but there was
well controlled delivery of the head. He had a tripletwisted cord, but cried within 30 seconds and appeared well, with Apgars of 71 and 95, respectively.
There was no evidence of sepsis during gestation or
delivery. Postnatal course was normal until the second day of life, when the infant was noted to be
irritable, cyanotic, and had clonic seizures of his
right hand.
He was transferred to a regional hospital, where
partial motor seizures involving the right arm progressing to a generalized convulsion lasting 10 minutes occurred. The seizure was successfully treated
with IV phenobarbital. A septic work-up was undertaken and the patient was treated prophylactically
with antibiotics. Lumbar puncture revealed bloodstained cerebrospinal fluid (CSF).
The infant was transferred to the Provincial tertiary care pediatric center. He appeared irritable
but was otherwise well; head circumference was
35.25 cm and the anterior fontanel was not bulging;
weight was 3240 g. Neurologic examination revealed normal motor function in all extremities;
reflexes were normal and symmetrical. General
physical examination was within normal limits. Pe© 2003 by Elsevier Science Inc.
360 Park Avenue South, New York, NY 10010 –1710

MCA Aneurysm in a Neonate

CT scan (3rd day of life) showing subarachnoid
hemorrhage predominantly in the left Sylvian
fissure.

1

ripheral blood hemoglobin concentration was 200
g/liter, and white blood cell count was 95000/mm3.
Cranial sonography, followed by computed tomography (CT), on the third day of life, showed
early ischemia in the left cerebral hemisphere, in
the territory of the MCA. There was also evidence of
subarachnoid hemorrhage (SAH), with predominance of blood in the left Sylvian fissure (Figure 1).
Ultrasound examination revealed a rounded hypodense (relative to the hemorrhage) lesion, highly
suggestive of an aneurysm.
During the patient’s 3-week hospital stay, seizures were well controlled with anticonvulsants
and he was seizure free after the first 2 days of
admission. He was discharged home without any
medication.
A week later, the infant presented with recurrent
convulsive seizures and apneic episodes. Skin was
pale, gray, and mottled. Theophylline, anticonvulsants and antibiotics were administered after blood
cultures were obtained. He required endotracheal
intubation, and continuous positive pressure
ventilation.
On examination, the infant’s weight and head circumference were 3980 g and 37.5 cm, respectively.
The anterior fontanel was full, but not bulging. Suck
reflex was weak; the left pupil was dilated and nonreactive to light. Hypertonia, particularly in the upper extremities, and opisthotonic posturing of the
trunk were noted. Reflexes were brisk bilaterally.
The remainder of the general and neurologic examination was negative.
Cranial ultrasound examination showed extension of the hemorrhage in the left cerebral hemisphere with mass effect and enlargement of the
aneurysm. Cranial CT confirmed the extension of

Surg Neurol 115
2003;59:114 –9

hemorrhage and infarction in the left MCA territory
(Figure 2). Cerebral angiography showed a large
aneurysm of the left distal middle cerebral artery
(Figures 3 and 4). Vasospasm was evident.
At surgery, it was necessary to remove most of
the left cerebral hemisphere, as it was swollen,
hemorrhagic, and necrotic. During the process of
removal, a branch of the MCA had to be clipped.
The MCA and distal branches were in marked
spasm.
The aneurysm was successfully clipped and excised. The aneurysm measured 1 cm in length and
had a narrow base, measuring 3 to 4 mm.
The wall was thin, similar to that of an aneurysm
in a adult. There was vigorous blood loss during the
procedure and the patient suffered an episode of
electromechanical myocardial dissociation; cardiac
resuscitation was successful. Postoperative recovery was uneventful.
Bilateral third nerve paresis and spastic tetraparesis persisted after surgery; the infant remained
severely disabled with marked spasticity of all 4
limbs, and was in a vegetative state until he died 4
years later.
PATHOLOGY
The surgical specimen consisted of blood clot and
temporal lobe fragments, and one abnormal vessel.
Representative pieces were embedded in parraffin
and serial sections were made. H & E stains were
done. The sections taken from the aneurysm, that
is, the cap portion, showed a thin-walled vessel
consisting mostly of adventitial type connective tissue. In some sections, the wall was extremely disrupted. Most of the aneurysm was filled with old
and new clot with obvious laminations in one portion. The other specimens were either blood clot
and/or pieces of cortical tissue that showed the

2

CT scan (7th day of life) extension of hemorrhage
with infarction of the MCA territory.

116 Surg Neurol
2003;59:114 –9

3

Maroun et al

Anteroposterior cerebral angiogram: distal MCA
aneurysm.

presence of
macrophages.

numerous

hemosiderin

laden

diagnosis of an internal carotid artery aneurysm
was made when the child was 9 months old. Grode
et al [7] reported a case of a young female whose
symptoms were lethargy, vomiting, and pallor on
the eighth day of life. SAH was not identified until
the child was about 5 weeks old. Angiography, at 8
weeks of age, demonstrated a left MCA aneurysm.
They concluded it was a congenital saccular
aneurysm.
Differences between intracranial aneurysms in
children as compared with adults have been extensively discussed. In early childhood aneurysms differ in their sex predominance, location, and size at
presentation. Of the 15 cases included in this review, 8 were male, 6 were female, and the sex of 1
case was unknown; thus there is a male predominance, with a ratio of 4:3. The aneurysm site was the
middle cerebral artery (6/15 or 40%) or the vertebrobasilar system (5/15 or 33%). Three aneurysms
were found on the internal carotid artery, anterior
communicating artery, and anterior cerebral artery.
The incidence of large (1.0-2.5 cm) or giant (⬎2.5
cm) aneurysms was 10/15 or 67%. Presenting symptoms included irritability, vomiting, seizures, SAH,
and coma. Subarachnoid hemorrhage is the most
common presentation. These findings are consistent with previous studies on early childhood
aneurysms.

Discussion
Intracranial aneurysms in the pediatric population
account for only 0.5 to 4.6% of all aneurysms [26].
McDonald and Korb [17] reviewed 1125 cases of
saccular cerebral aneurysms; 17 (1.5%) occurred in
children, only one of whom was younger than 18
months. Laitinen [13] reported a similar childhood
incidence of 1.3% in 688 patients. Patel and Richardson [22] reviewed 3000 cases of SAH including
58 cases in patients under 19 years of age, the
youngest was 8 years old. In the Cooperative Study
[16], only one of 2627 cases reviewed was in the 0 to
4 year age group. Nishio et al [21] reviewed 66 cases
of cerebral aneurysms in children under 2 years of
age.
Aneurysms in the neonate are even rarer. Ferrante et al [3] found only 8 cases in the first 4 weeks
of life. In our review of the literature, we found 15
cases, including our own, of cerebral aneurysms in
the neonatal period (Table 1). Two other cases
were reported in a 42 and 45 mm embryo [1]. Also,
not included in the neonatal data, is a case reported
by Thompson and Pridham [30] of an infant female
who developed opthalmoplegia and quadriparesis
at 2 weeks of age. Initial LP was clear. However,

4

Lateral cerebral angiogram: diffuse cerebral spasm
with aneurysm.

Irritable, cyanotic, SZ, SAH
d-MCA (1 cm)
*dna ⫽ data not available.

3 days
Present Case

M

Hematoma on CT
SAH, IVH
d-MCA (6 mm)
ACA (10 mm) Fusiform
1 month
11 days
Thrush and Mirano (1988)
Tan et al (1998)

F
M

4 days
24 days

Jones and Shearburn (1961)
Wierdis et al (1965)
Pickering et al (1970)
Lee et al (1978)
Lipper et al (1978)
Hungerford et al (1981)
Shimauchi et al (1989)

Kuchelmeister et al (1993)
Hosotani et al (1995)

M
M

ACommA (10 mm)
d-PICA (large)

SZ, SAH
SAH

No surgery. Died.
No surgery. Died.
Neck clipped. Did well.
No surgery. Did well.
No surgery. Died.
No surgery. Died.
No surgery. Died.
Excision. Did well.
Parent artery clipped.
Did well.
No Surgery. Did well.
Parent artery clipped.
Did well.
Clipped. Did well.
Unsuccessfully clipped.
Did well.
Clipped & excised.
SAH after minor head trauma
Cyanotic at birth, SAH.
Irritable, SZ, SAH coma
SAH
Apnea, cyanosis, SAH, SZ
SZ, SAH
SAH
Irritable, vomiting, SAH
SAH, hematoma
Circle of Willis (dna)*
PCA-PCommA (2 mm)
MCA (large)
MCA (dna)*
d-PICA (2.5 cm)
BA (3 cm)
ICA (dna)*
d-MCA (1.5 cm)
MCA (10 mm) Fusiform
23 days
64 hr.
4 wk.
Newborn
1 month
13 days
10 days
1 month
19 days
Newcomb and Munns (1949)

M
M
F
dna
M
F
F
F
F

AGE

SEX

Surg Neurol 117
2003;59:114 –9

REFERENCE

1

Clinical Features of Neonatal Cerebral Aneurysms

SITE (SIZE)

PRESENTATION

OUTCOME

MCA Aneurysm in a Neonate

One of the striking findings from Table 1 is the
low operative mortality. An exception was the case
presented by Tan et al [29]. They described an
11-day-old infant with an anterior cerebral artery
aneurysm, who died 2 weeks after an unsuccessful
attempt at clipping the aneurysm. Further, with the
exception of one case, mortality in patients who
were not treated surgically was high. Piatt and
Clunie [23] reported a male neonate with a superior
cerebellar artery aneurysm who was managed conservatively and did well. In our case, the patient was
initially managed conservatively. However, he presented again a week later, at which time cranial
ultrasound and CT showed extension of hemorrhage and infarction in the left cerebral hemisphere. This might have been prevented if the clot
had been evacuated and the aneurysm clipped
earlier.
The prognosis for ruptured aneurysms in the
early neonatal period is poor, despite the greater
capacity of the infantile nervous system for recovery. Early diagnosis enhances favorable prognosis.
Therefore, surgeons should have a high index of
suspicion and perform appropriate investigations
when an infant presents with symptoms of increasing irritability, vomiting, and/or seizures, and an LP
yields bloody CSF. The most important first step in
diagnosis is a cranial ultrasound. In our case, initial
ultrasound investigation at 3 days of age revealed
hemorrhage in the left Sylvian fissure and a
rounded area suggestive of an aneurysm. Repeat
examination carried out at 21⁄2 weeks of age showed
extension of the hemorrhage and enlargement of
the aneurysm. Our delay in the management of this
particular patient was multifactorial. He was being
treated in the Neonatal Unit and we were only asked
to see him a week later. Because of the fact that
there was early ischemia indicating cerebrovascular spasm, we elected to wait before doing the angiogram and surgical clipping. However, we feel
now that the treatment should have been much
quicker and clipping should have been conducted
earlier. Cranial sonography is a noninvasive technique that can be repeated without sedation or risk
of radiation. Ismail et al [10] report that it is an
invaluable diagnostic tool that can demonstrate the
location and size of an intracranial hemorrhage and
delineate the size or distortion of the ventricular
system, as well as suggest the presence of an aneurysm. However, it may miss superficial AVMs or
small aneurysms around the circle of Willis.
CT, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) are also useful
in the diagnosis of intracranial aneurysms in the
neonate. CT is very sensitive for acute hemorrhage,

118 Surg Neurol
2003;59:114 –9

but is not specific enough to identify the cause of
the hemorrhage. It may show a focal hyperdense
mass with or without enhancement in addition to
the hemorrhage. MRI demonstrates the hemorrhage and may show a focal mass with a different
signal than the surrounding hemorrhage, with or
without flow-void or enhancement. MRA correlates
well with conventional angiograms and may eventually replace it. MRA can demonstrate aneurysms
as small as 3 mm [29]. A major role of MRA in the
future may be in screening patients at high risk for
developing aneurysms (e.g., those with a family history of aneurysms). Cerebral angiography carries
significant risk in the neonate, but remains the gold
standard for preoperative imaging.
A major controversy concerning etiopathogenesis is whether cerebral aneurysms are congenital or
acquired. In 1930, Forbus [4] proposed that aneurysms are acquired lesions, arising from a combination of a congenital medial defect of the arterial
wall and degeneration of the internal elastic lamina.
He suggested this theory when he observed a medial defect at the apex of cerebral artery bifurcations and found that an aneurysm appeared to arise
as a bulging through the medial defect. Since then,
much conflicting evidence has been presented.
Glynn [6] has shown that arteries can withstand
intraluminal pressures of 400 to 600 mm Hg without
showing any local bulging of the intima into the
space lacking the media. Furthermore, medial defects are very common in comparison to the relatively small number of cerebral aneurysms in the
general population [2,6,26]. Medial defects also increase with age.
The site of medial defects and aneurysms differ.
Medial defects are also found in species that do not
develop aneurysms. Thus, medial defects may not
be congenital in origin nor represent Forbus’ proposed “locus minoris resistentiae.”
A recent study carried out by Futami et al [5] in
rats showed a disparity between the location of the
aneurysm and medial defects. They proposed that
the intimal pad is the primary cause of aneurysms,
with the medial defect a factor contributing to the
degeneration of the internal elastic lamina. The authors postulate that the presence of the intimal pad
may cause aneurysmal development by causing
stresses in the wall at that point secondary to muscle cells in the pad and media acting in different
directions, by producing stagnation of blood flow
behind the intimal pad affecting nutrition of the
wall, or by causing turbulence and shear stress in
that area with the production of endothelial substances that cause degeneration of the vessel wall.
Further work on the role of intimal pads in aneu-

Maroun et al

rysm formation will likely be a topic of future
research.
Other authors postulate that cerebral aneurysms
are congenital in nature. Bremer [1] suggested that
aneurysms may be remnants of fetal cerebral plexuses. He thought that during development, the
proximal portion of such plexuses enlarges, while
the distal segments degenerate and thus produce
aneurysmal sacs. Further support for congenital
formation of aneurysms arises from the occurrence
in young persons with a higher frequency occurring
in the first 2 years of life [3], familial occurrence
[11], association with other cerebral and vascular
congenital anomalies, and variations in the Circle of
Willis. Furthermore, limited data from light microscopy studies, including our case, has shown fragmentation or absence of both the internal elastic
lamina and smooth muscle within the aneurysmal
sac. These features are similar to those seen in
saccular aneuryms of the adult.
Stehbens [26,27] has refuted the evidence suggesting a primary congenital mechanism as the
cause of pediatric aneurysms. He stated that true
saccular aneurysms in childhood are rare, and that
the presence of a few cases does not negate the
acquired degenerative nature of most cases. He further stated that the presence of so-called vestigial
vessels has not been demonstrated, and that the
presence of a few familial cases is to be expected
given the frequency of aneurysms in the population.
Also, variations in the Circle of Willis are frequently
seen in other animals, whereas aneurysms are not
[32].
Nishio et al [21] emphasized the role of hemodynamic factors in the development of aneurysms in
adults and infants. In adults, hemodynamic stress
against a background of degenerative arterial wall
changes is proposed to be the underlying cause of
aneurysms. In infants, they postulate that the embryonic development of cerebral vessels in association with hemodynamic factors influences the development of aneurysms. The MCA appears earlier
than other vessels, supplies more blood flow to the
developing cerebral hemispheres, and is exposed
to the hemodynamic stress of direct blood flow for
a longer period of time than other vessels. This may
be an explanation for the common occurrence of
MCA aneurysms in neonates. Piatt and Clunie [23]
have suggested that the more common occurrence
of posterior circulation aneurysms in neonates is
attributable to trauma, with compression of vessels
against the free edge of the tentorium during the
birth process. Vascular damage later gives rise to
aneurysm formation.
In our patient, the aneurysm was considered to

MCA Aneurysm in a Neonate

be congenital because of the occurrence of a single
large distal MCA aneurysm that by history, had
been present since birth. This would make an acquired pathogenesis extremely unlikely. We recommend the routine use of cranial ultrasonography if
a cerebral aneurysm is suspected in a neonate, with
early clot evacuation and clipping of the aneurysm.
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