Child's Nerv Syst (1993) 9:302-305
m/ NS
A probably familial saeeular aneurysm
of the anterior communicating artery in a neonate
K. Kuchelmeister 1, R. Schulz 2, M. Bergmann 1, R. Schwuchow z, E. Vollmer 3
1 Institut fiir Neuropathologie der Universit/it, Domagkstrasse 17, D-48129 Mfinster, Germany
2 Kinderabteilung des St. Elisabeth-Krankenhauses, Friedrich-Ebert-Strasse 59, D-56503 Neuwied, Germany
3 Institut •r Pathologie der Universit/it, Domagkstrasse 17, D-48129 Miinster, Germany
Received: 8 July 1992/Revised: 20 October 1992
Abstract. A 3 2 - d a y - o l d b o y d i e d of r e c u r r i n g c e r e b r a l
h e m o r r h a g e s s t a r t i n g o n the 4th d a y of life. A u t o p s y dis-
c l o s e d a r e m i t t i n g l y r u p t u r e d s a c c u l a r a n e u r y s m of the
a n t e r i o r c o m m u n i c a t i n g artery. A 7 - d a y - o l d b r o t h e r of
his h a d p r e v i o u s l y d i e d of r e c u r r i n g s u b a r a c h n o i d h e m o r -
rhages as well. T h e y o u n g age of the patient, the site of
the a n e u r y s m , a n d its p r o b a b l y familial o c c u r r e n c e m a k e
this case a u n i q u e one. N o n a n e u r y s m a t i c b a s a l c e r e b r a l
arteries s h o w e d r e m a r k a b l e h i s t o l o g i c a l c h a n g e s p a r t l y
r e s e m b l i n g t h o s e seen in f i b r o m u s c u l a r d y s p l a s i a , s o m e of
them probably representing preaneurysmatic alterations.
A k n o w n u n d e r l y i n g systemic disease c o u l d n o t be found,
a n d i m m u n o h i s t o c h e m i c a l d e t e c t i o n of t y p e I I I c o l l a g e n
r e v e a l e d n o identifiable deficiency.
Key words: N e o n a t a l i n t r a c r a n i a l a n e u r y s m - C e r e b r a l
a n e u r y s m in c h i l d h o o d - F a m i l i a l i n t r a c r a n i a l a n e u r y s m -
Collagen type III- Cerebral hemorrhage
Introduction
C e r e b r a l s a c c u l a r a n e u r y s m s in the p e d i a t r i c age g r o u p
are r a r e [1, 2, 10, 17]. I n e a r l y c h i l d h o o d t h e y are yet m o r e
infrequent [7], a n d in the 1 st m o n t h of life especially t h e y
are e x t r e m e l y u n c o m m o n [7, 15]. I n this age g r o u p , a n e u -
r y s m s of the a n t e r i o r c o m m u n i c a t i n g a r t e r y a r e p a r t i c u -
l a r l y r a r e [19]. O n l y a few cases of familial i n t r a c r a n i a l
a n e u r y s m s have been r e c o r d e d in c h i l d r e n [30]. W e r e p o r t
a u n i q u e case of a p r o b a b l y familial s a c c u l a r a n e u r y s m of
the a n t e r i o r c o m m u n i c a t i n g a r t e r y c a u s i n g r e c u r r i n g in-
t r a c r a n i a l h e m o r r h a g e s in a n e o n a t e .
Case report
The patient was the third child of 28-year-old parents. They are
healthy, except for an allergic diathesis in the mother. The mother's
grandfather had suffered from epilepsy, and the father of her hus-
Correspondence to: K. Kuchelmeister
9 Springer-Verlag 1993
band has arterial hypertension. The 4-year-old brother of our pa-
tient is healthy, but another brother (born 22 months prior to the
third child) had died on his 7th day of life due to recurring subarach-
noid hemorrhages. Gestation, delivery, and the early postnatal
course of this full-term infant were reported to be uneventful, when
on the 3rd day of life his condition suddenly deteriorated. Lumbar
puncture revealed sanguineous liquor. Another subarachnoid hem-
orrhage occurred on the 6th day of life, and the child died the next
day. Autopsy confirmed massive subarachnoid hemorrhage, the
origin of which could not be determined due to severe tissue destruc-
tion. Further information was not available.
Our patient was born spontaneously in the 39th week of an
uneventful gestation (birth weight 3870 g). He had a double-twisted
cord, but his Apgar score was unremarkable. The postnatal course
had been normal until the 4th day of life, when suddenly aspiration
and apnea occurred.
The infant was intubated and transferred to a perinatal ~ntensive
care unit. Except for hyponatriemia, initial laboratory tests were
unremarkable. During the first days recurring seizures with oral
automatisms and later muscular hypotonia, reduced spontaneous
motor activity, and sometimes poor crying were observed. Initial
ultrasound examination revealed hyperechoic structures on the
floor of both frontal horns. There was increasing hydrocephalus,
and intraventricular hemorrhage was presumed. Ultrasonography
on the 13th day of life showed a mass between the frontal horns
resembling hemorrhages into a cavum septi pellucidi and a pre-
sumptive Dandy-Walker cyst. Nine days later, magnetic resonance
imaging revealed hemorrhages over both hemispheres, into the
basal cisternae and the interhemispheric fissure, into the ventricles
and into a cavum septi pellucidi (Fig. 1). The ventricles were dilated.
Agenesis of the corpus callosum and a cerebellar malformation with
aplasia of the caudal hemispheric parts and of the inferior vermis
were suspected.
After a 10-day course of antibiotic treatment for aspiration
pneumonia, the child was extubated. On the 29th day of life he
suddenly deteriorated again. Ultrasonography showed a new intra-
ventricular hemorrhage. Following a further cerebral hemorrhage
the boy died on his 32nd day of life.
Autopsy was confined to the brain (weight 500 g). There were
fresh and older hemorrhages in the basal cisternae, in the sylvian
fissures, the interhemispheric fissure, and in the cisterna ambiens.
Blood masses in the cerebellomedullary cisterna had caused com-
pression and upward displacement of the cerebellum, which showed
no malformation. There was a saccular aneurysm of the anterior
communicating artery, 1 cm in diameter, which had repeatedly rup-
tured at its dorsal surface (Fig. 2). No other aneurysms and no
anomalies of the circle of Willis were seen. The ventricles were
markedly dilated and contained many blood clots. There was hem-

Fig. 3. The internal elastic lamina and the media stop abruptly at
the neck of the aneurysm (arrows). There is focal absence or thin-
ning of the media in the anterior communicating artery (arrow-
heads). The vessel is surrounded by blood masses and siderophages.
There is a thrombus in the lumen of the aneurysm (asterisk). (Elas-
tica-van Gieson stain; original magnification x 16)
orrhage into a cavum septi pellucidi (Fig. 2). The corpus callosum
was extremely thinned due to ventricular dilation; some microcysts
were seen in the cerebral white matter.
Histological examination disclosed siderosis of the superficial
cerebral cortical layers and of the ventricular walls, and focal necro-
sis of the cerebral white matter due to edema. The internal elastic
lamina and the media, which was focally thinned or completely
absent in the aneurysm-bearing part of the artery, stopped abruptly
at the neck of the aneurysm (Fig. 3). The aneurysm wall contained
deposits of blood pigment and consisted of fibrous tissue, rich in
small, often elongated, obviously fibroblastic cells. Its internal part
seemed to correspond to the intima and its external part to the
media of the artery; the lumen of the aneurysm was filled with
thrombi (Fig. 3).
Apart from unremarkable findings histological sections of non-
aneurysmatic basal cerebral arteries disclosed in some areas focal
absence of the internal elastic lamina either as a narrow or as quite
a broad gap (Fig. 4A). Sometimes there was also a slight focal
thickening of the intima (Fig. 4 A) or a focal thinning or absence of
the media (Fig. 4A, B). Some slides showed changes resembling
fibromuscular dysplasia: the intima was broadly thickened with
severe narrowing of the vessel lumen; the internal elastic lamina was
absent in large parts of the transverse section, and the media was
often markedly thinned (Fig. 4 C). Such changes were not seen in
basal cerebral arteries of two age-matched control patients who had
died of sudden infant death syndrome. There were no inflammatory
vessel changes. Immunohistochemical detection of collagen type III
303
Fig. 1. Magnetic resonance imaging shows
masses of blood in the ventricular system, a
cavum septi pellucidi, the interhemispheric fis-
sure, and the basal cisternae. Marked dilation
of the ventricles and hypointensity of the peri-
ventricular white matter are seen
Fig. 2. Autopsy discloses a repeatedly ruptured,
partially thrombosed aneurysm of the anterior
communicating artery (arrow). There are blood
clots in the ventricular system and interhemi-
spheric fissure and hemorrhages in the basal
leptomeninges
(polyclonal antibody was a generous gift from Dr. Y. Ueda, Insti-
tute of Pathology, University of M/inster) disclosed a strong posi-
tivity in the aneurysm wall. There was also a strong immunoreactiv-
ity in the other basal cerebral arteries of our patient, predominantly
in the adventitia. This staining was indistinguishable from the label-
ing in the cerebral arteries of the two control cases.
Discussion
This case is in m a n y respects e x t r e m e l y unusual. A cere-
b r a l s a c c u l a r a n e u r y s m in such a y o u n g child is a very
infrequent finding: i n t r a c r a n i a l a n e u r y s m s in the p e d i -
atric age g r o u p r e p r e s e n t o n l y a p p r o x i m a t e l y 0 . 5 % -
4 . 6 % o f all cases [17]. N i s h i o et al. [19] r e c o r d e d a t o t a l of
66 cases of c e r e b r a l s a c c u l a r a n e u r y s m s in c h i l d r e n u n d e r
the age of 2 years. I n n e o n a t e s in the 1 st m o n t h of life t h e y
are still very m u c h r a r e r : reviewing 72 cases in c h i l d r e n
u n d e r 5 years, F e r r a n t e et al. [7] f o u n d 8 such cases. I n
four reviews of the l i t e r a t u r e [7, 8, 13, 15], o n l y 12 cases
(including two fetal cases) in infants n o t o l d e r t h a n
1 m o n t h have been r e p o r t e d .
A n e u r y s m s in the p e d i a t r i c age g r o u p often o c c u r in
u n u s u a l l o c a t i o n s c o m p a r e d to the a d u l t p o p u l a t i o n [1, 2,
10, 17], a n d thus the site of the a n e u r y s m in o u r case is
a b s o l u t e l y o u t of the o r d i n a r y : while the a n t e r i o r c o m m u -
n i c a t i n g a r t e r y is a m o n g the m o r e c o m m o n l o c a t i o n s of
i n t r a c r a n i a l s a c c u l a r a n e u r y s m s in adults, this site was
f o u n d in o n l y 4 c h i l d r e n u n d e r 2 years of age [19]. T h e
y o u n g e s t was 11 m o n t h s old [4], a n d n o n e of the 12 neo-
n a t a l a n e u r y s m s referred to a b o v e was l o c a t e d on this
artery.
A l t h o u g h it has n o t been p r o v e n t h a t the s u b a r a c h -
n o i d h e m o r r h a g e s of o u r p a t i e n t ' s b r o t h e r were also
c a u s e d b y a n a n e u r y s m , in r e t r o s p e c t this seems very like-
ly. Therefore, a familial o c c u r r e n c e of the a n e u r y s m s c a n
be a s s u m e d . A l t h o u g h familial i n t r a c r a n i a l a n e u r y s m s
t e n d to cause s y m p t o m s at a n earlier age t h a n t h o s e in the
general p o p u l a t i o n [12, 16, 20, 22], ter Berg et al. [30]
f o u n d o n l y five p a t i e n t s u n d e r 20 years of age with a
familial c e r e b r a l a n e u r y s m . T h e y o u n g e s t was a girl w h o
suffered c e r e b r a l h e m o r r h a g e at the age of 4 years [30].
T h e fact t h a t the h e m o r r h a g e s h a d o c c u r r e d so very early
in b o t h o u r p a t i e n t a n d his b r o t h e r is p a r t i c u l a r l y u n u s u -
al. A s s u m i n g a familial o c c u r r e n c e of the a n e u r y s m , its
site on the a n t e r i o r c o m m u n i c a t i n g a r t e r y is even m o r e
304
uncommon: this location is clearly more infrequent in
familial cases than in sporadic ones [12, 16].
Nevertheless, there are many open questions concern-
ing the familial occurrence of intracranial aneurysms.
Cerebral saccular aneurysms may be more frequent in
patients with certain diseases with defects in connective
tissue and/or alterations of cerebral blood flow where
hereditary etiological factors are known to exist: for ex-
ample, type IV Ehlers-Danlos syndrome, Marfan's syn-
drome, pseudoxanthoma elasticum, and polycystic kid-
ney disease [16, 20]. They may also be associated with
other anomalies where hereditary factors are not so clear,
such as coarctation of the aorta, arteriovenous malforma-
tions, and fibromuscular dysplasia [26, 30]. We have no
information about the occurrence of such diseases in the
families of our patient, and there are no clinical indica-
tions of their presence in the boy himself except for fibro-
muscular dysplasia-like histological changes referred to
below.
In familial cerebral aneurysms without such under-
lying diseases, the occurrence in members of the same
family may sometimes be only fortuitous [3, 29]. In our
cases, however, this seems rather unlikely. Other cases are
suggestive of a dominant pattern of inheritance [9, 12, 27],
but often a multifactorial transmission has been supposed
[3, 11]. Unknown hereditary connective tissue disorders,
perhaps affecting metabolism of connective tissue proteins,
may play a pathogenetic role in some cases of familial
cerebral aneurysm [16, 29]. The collagens might be im-
portant in this respect: in type IV Ehlers-Danlos syn-
drome, where intracranial aneurysms can occur [25], lack
of type III collagen has been detected [23], and several
authors [6, 18, 21] described a minor deficiency of this
collagen in some patients with (sporadic) cerebral saccu-
Fig. 4 A- C. Histological changes
of nonaneurysmatic basal cerebral
arteries. A Defects of the internal
elastic lamina (arrows); focal thin-
ning of the media (curved arrow)
and focal thickening of the intima
(asterisk). B Absence or thinning
of the media (arrows) in two fur-
ther arteries. C Nearly complete
occlusion of an artery by massive
thickening of the intima. The in-
ternal elastic lamina is only rudi-
mentarily present (arrows); in
these areas the media is markedly
thinned. (Elastica-van Gieson
stain; original magnifications:
A • B x20.5, C •
lar aneurysms. Leblanc et al. [14], however, did not find
such a deficiency in a patient with three cerebral aneu-
rysms whose mother and sister also had intracranial
aneurysms. Our immunohistochemical findings with an
antibody against type III collagen do not support the
idea that deficiency of this protein is a relevant patho-
genetic factor either, but nevertheless, qualitative disor-
ders of this collagen cannot be excluded.
While the aneurysm itself showed a typical histo-
morphology [28], the histological changes in some other
basal cerebral arteries are remarkable. The alterations
resembling fibromuscular dysplasia may be important
because cerebral aneurysms can be associated with this
disease, which may involve intracranial arteries [24].
Interestingly, the youngest infant apart from ours with
an anterior communicating artery aneurysm was an
11-month-old boy with fibromuscular dysplasia of the
renal and cerebral arteries [4]. Should our case indeed
represent a form of this disease, however, the question of
etiology would still not be answered, as the cause of fibro-
muscular dysplasia is not exactly known [24].
Some of the histological arterial changes have proba-
bly to be regarded as preaneurysmatic alterations, since
(acquired or congenital) defects of the internal elastic
lamina are of great importance in aneurysm formation
[26, 29]. Thus, it may be speculated whether our patient
would have developed multiple intracranial aneurysms in
later life. The l 1-month-old boy reported by Cedzich
et al. [5] may represent a more advanced example of a
similar case. He had subarachnoid hemorrhage due to a
large saccular aneurysm of the left middle cerebral artery,
and during operation multiple minute aneurysms of this
vessel were seen which histologically proved to be aneu-
rysms in statu nascendi.

Acknowledgements. We would like to thank Mrs. Dr. U. Gropp-
Merl, Bad Honnef, for clinical information, Dr. K.-O. Bartz
(pathologist), Neuwied, for providing the tissue material, and Dr.
H. P. Kurtenbach, Koblenz, for the magnetic resonance image. We
are indebted to Ms. M. Leisse and Ms. C. Schliiter for technical
assistance, Mrs. H. Gerdes-Funnek6tter for photographic services,
and Mrs. S. Potapczuk for linguistic help.
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