Neurol Med Chir (Tokyo) 42, 391395, 2002

De Novo Cerebral Aneurysms Manifesting as Repeated

Subarachnoid Hemorrhage and Cerebral Ischemic Stroke
Case Report

Hirokatsu OSAWA, Kazuhiro FUKUI, Goro OTSUKA, Ken-ichi HATTORI,

Tatsunari SATAKE*, and Motoko MIYAZAKI

Departments of Neurosurgery and *Pathology, Nagoya Ekisaikai Hospital, Nagoya

Abstract
A 29-year-old man suffered repeated subarachnoid hemorrhage and cerebral ischemic stroke over a
period of 6 years. Cerebral angiography at each episode disclosed development of multiple de novo
aneurysms at the bilateral middle cerebral arteries (MCAs), internal carotid arteries, right anterior
cerebral artery, and right vertebral artery. Two of the ruptured aneurysms were treated by surgical and
endovascular treatment, but he died of the effects of rupture of a de novo right MCA aneurysm. Histo-
logical examination at autopsy disclosed marked degenerative changes in all layers of the cerebral ves-
sels, which were probably congenital in origin.
Key words: de novo aneurysm, subarachnoid hemorrhage, cerebral ischemic stroke,
hypertrophy of intima, neuroradiological follow up

Introduction newly developed lesions. Cerebral angiography

De novo aneurysm is a newly formed aneurysm
developing from a cerebral artery which previously
appeared normal on angiography.5) The de novo
aneurysm is comparatively rare and the annual inci-
dence is 0.891.8%.3,18,19) The interval between the
first angiography and occurrence is 3 to 20 years.17)
We treated a patient who presented with multiple
de novo aneurysms located on almost all of the
cerebral arteries associated with repeated subara-
chnoid hemorrhage (SAH) and cerebral ischemic
stroke.
showed narrowing of the bilateral vertebral arteries
(VAs) and basilar artery, and multiple aneurysms of
the left MCA and internal carotid artery (ICA)
(Fig. 2). He was treated medically.
He suffered sudden onset of headache and was
transferred to our hospital on April 13, 1998. CT
showed SAH, and cerebral angiography revealed
a de novo left posterior communicating artery

Case Report
A 29-year-old man with no past and familial history
suffered SAH due to rupture of a left middle cerebral
artery (MCA) aneurysm on April 19, 1994 (Fig. 1
left). He developed vasospasm after clipping of the
aneurysm (Fig. 1 right), but returned to normal so-
cial life after 1 month.
He presented with right hemiparesis, right cere-
bellar ataxia, and right sensory disturbance on July Fig. 1 Oblique left carotid angiogram (left) show-
5, 1997. Computed tomography (CT) detected no ing the ruptured aneurysm in the M2 portion
(arrow). Postoperative left carotid angio-
Received December 20, 2001; Accepted June 14, gram (right) demonstrating complete clip-
2002 ping of the aneurysm.

391
392 H. Osawa et al.
Fig. 2 Follow-up lateral left carotid angiogram
(left) revealing multiple de novo aneurysms
of the left middle cerebral artery and inter-
nal carotid artery. Lateral left vertebral an-
giogram (right) showing irregular narrow-
ing of the vertebral and basilar arteries.
Fig. 3 Lateral left carotid angiogram (left) showing
a de novo left posterior communicating ar-
tery aneurysm. Postoperative lateral left
carotid angiogram (right) revealing
Guglielmi detachable coils in the posterior
communicating artery aneurysm.
aneurysm (Fig. 3 left). The aneurysm was considered
to have ruptured based on the CT findings, and was
treated with Guglielmi detachable coils (GDCs)
(Fig. 3 right). He underwent ventriculoperitoneal
shunt for hydrocephalus, and was discharged
without neurological deficit.
He suffered repeated transient ischemic attacks
about every 3 months from August 1999 to June
2000, manifesting as diplopia, right ptosis, right
facial nerve paresis, and right hemiparesis. CT and
cerebral angiography at each event revealed no
remarkable changes.
Follow-up angiography showed development of
de novo aneurysms of the right anterior cerebral ar-
tery (ACA) and right MCA on August 8, 2000 (Fig. 4).
He suffered sudden onset of headache and CT
showed third SAH on August 29, 2000. He was treat-
ed conservatively because cerebral angiography
Fig. 4 Follow-up anteroposterior (upper left) and
lateral (upper right) right carotid angio-
grams demonstrating several aneurysms
(arrows) of the middle cerebral artery and
anterior cerebral artery. Anteroposterior
(lower left) and lateral (lower right) left
carotid angiograms revealing multiple
aneurysms on both branching and non-
branching locations of the middle cerebral
artery and internal carotid artery.
could not identify the ruptured aneurysm responsi-
ble for the SAH. He suddenly became comatose on
September 12, and CT revealed massive right frontal
intracerebral hemorrhage. He died on September 13
of progressive brain damage.
Autopsy examination found that the left MCA and
ICA branches were irregularly dilated, with multiple
saccular and fusiform aneurysms on both branching
and non-branching locations of the bilateral MCAs,
bilateral ICAs, right ACA, and right VA-posterior in-
ferior cerebellar artery (Fig. 5A).
Histological examination found that the lumens of
almost all vessels were partially narrowed by hyper-
trophy of the arterial intima. In particular, the thick-
ened intima contained laminar structures. The ar-
terial media contained fewer smooth muscle cells
and increased fibrosis in almost all vessels. The
walls between the aneurysms and the parent arteries
Neurol Med Chir (Tokyo) 42, September, 2002
 De Novo Cerebral Aneurysms 393

Fig. 5 A: Autopsy photograph showing multiple saccular and fusiform aneurysms in the areas of the
bilateral middle cerebral arteries (MCAs) and internal carotid arteries, right anterior cerebral
artery (ACA), and right vertebral artery (VA)-posterior inferior cerebellar artery. Guglielmi
detachable coils (arrow) are seen at the left internal carotid artery-posterior communicating
artery and a clip (arrowhead) at the left MCA. BA: basilar artery. BD: Photomicrographs of
cerebral artery sections taken at autopsy showing (B) intimal hypertrophy (I) and medial
fibrogenesis (M) in the internal carotid artery (elastica van Gieson stain, 40), (C) laceration
of the elastic lamina (arrow), thinning of medial smooth muscle cells with fibroplasia (M),
and invasion of monocytes in the right MCA aneurysm (elastica van Gieson stain, 40), and
(D) hematoma (H) and laceration of the vessel wall (arrow) at the rupture point of the right
MCA (elastica van Gieson stain, 200).

contained defects of the elastic lamina and arterial
media with fibroplasia. Almost all aneurysm walls
consisted of fibrous tissue, with a small number of
monocyte invading the aneurysm wall, but no
necrosis or organization of the wall was identified
(Fig. 5BD).
Discussion
Our patient presented with repeated development of
de novo saccular and fusiform aneurysms on nearly
all the cerebral vessels, manifesting as repeated SAH
and cerebral ischemic stroke, in contrast to previous
cases of de novo aneurysms which usually presented
as a small number of saccular aneurysms.3,18,19)
The normal structure of cerebral artery is differ-
ent from other artery. Cerebral artery manifests thin
arterial media, lack of external elastic lamina, and
insufficient adventia.9) For these reasons, arterial
media and internal elastic lamina play a key role in
protecting cerebral artery from blood pressure.4,20)
Mural degeneration of the vessel is the predisposi-
tion for the development of a saccular aneurysm
with subsequent growth due to distention of the ves-
sel wall lacking an appropriate internal elastic lami-
na.17) De novo aneurysms are formed by similar
mechanisms to other aneurysms. The risk factors for
de novo aneurysms include congenital factors such
as a medial defect and destruction of the elastic
lamina, and acquired factors such as change in

Neurol Med Chir (Tokyo) 42, September, 2002

394 H. Osawa et al.
hemodynamic stress, hypertension, smoking, and
atherosclerosis.6,17) The present case had both saccu-
lar and fusiform aneurysms on the vessels of the cir-
cle of Willis and peripheral vessels. This unusual
manifestation of multiple aneurysms suggests con-
genital degeneration of cerebral vessels.1)
Various congenital connective tissue disorders
including autosomal dominant polycystic kidney
disease, Ehlers-Danlos type IV syndrome, and von
Recklinghausen's neurofibromatosis type I are asso-
ciated with cerebral aneurysms.8) Alpha-1-antitryp-
sin deficiency and type 3 collagen deficiency may be
associated with the pathogenesis of cerebral
aneurysms.2,12) In our case, none of these diseases
were present. However, fibromuscular dysplasia
(FMD) could not be excluded because of the unusual
aneurysms located in both the branching and non-
branching sites.10) FMD is usually associated with
disruption of the medial smooth muscle layer and fi-
brous proliferation, but the present case showed
changes in the intimal rather than the medial wall.14)
Recently, intimal wall damage was reported in
FMD,7) suggesting that the present case was related
to FMD.
The ischemic symptoms in our patient were prob-
ably due to the partial narrowing of the lumen of
almost all vessels due to hypertrophy of arterial
intima. Distal migration of thrombus from the
aneurysms is another possible mechanism for the
ischemic symptoms.11) Hypertrophy of the cerebral
arterial wall may have prevented early rupture of the
aneurysms.15,20)
Surgical treatment for de novo aneurysm is not
curative because of recurrence and rupture in the
same or another of the cerebral arteries. Treatment
with GDCs can obliterate multiple aneurysms in
both the anterior and posterior circulation less inva-
sively in one session even in the acute phase of
hemorrhage,13) which is potentially useful for de
novo aneurysms.16) In our case, surgical or endovas-
cular treatment for all of the aneurysms was impos-
sible because of the high invasiveness of the re-
quired surgical approach and the unsuitability of
GDCs for wide neck fusiform aneurysms.
Regular neuroradiological follow up is essential
for younger patients with cerebral aneurysm con-
sidering the high risk of de novo aneurysm.21)
References
1) Belen D, Bolay H, Firat M, Akpinar G, Bertan V: Un-
usual appearance of intracranial fibromuscular dys-
plasia. Angiology 47: 627632, 1996
2) Brega KE, Seltzer WK, Munro LG, Breeze RE: Geno-
typic variations of type III collagen in patients with
cerebral aneurysms. Surg Neurol 46: 253257, 1996
3) David CA, Vishteh AG, Spetzler RF, Lemole M,
Lawton MT, Partovi S: Late angiographic follow up
review of surgically treated aneurysms. J Neurosurg
91: 396401, 1999
4) Glynn LE: Medial defects in the circle of Willis and
their relation to aneurysm formation. J Path Bacteriol
51: 213222, 1940
5) Graf CJ, Hamby WB: Report of a case of cerebral
aneurysm in an adult developing apparently de novo.
J Neurol Neurosurg Psychiatry 27: 153156, 1964
6) Kanemoto Y, Hisanaga M, Bessho H: De novo ver-
tebral artery-posterior inferior cerebellar artery
aneurysm: A case report. Surg Neurol 47: 473475,
1997
7) Mandai S, Nishino S, Itoh T, Motoki M, Norikane H,
Moriya Y, Matsumoto Y: [A case of fibromuscular
dysplasia associated with intra- and extracranial mul-
tiple aneurysms]. No Shinkei Geka 20: 611615, 1992
(Jpn, with Eng abstract)
8) Nekrysh SY: Association between heritable connec-
tion tissue disorders and intracranial aneurysms.
Surg Neurol 54: 7778, 2000
9) Oneda G: [Pathology of cerebral hemorrhage
(author's translation)]. Nitibyokaisi 59: 2756, 1970
(Jpn)
10) Osborn AG, Anderson RE: Angiographic spectrum of
cervical and intracranial fibromuscular dysplasia.
Stroke 8: 617626, 1977
11) Qureshi AI, Mohammad Y, Yahia AM, Luft AR,
Sharma M, Tamargo RJ, Frankel MR: Ischemic
events associated with unruptured intracranial
aneurysms: Multicenter clinical study and review of
the literature. Neurosurgery 46: 282290, 2000
12) Schievink WI, Katzmann JA, Piepgras DG, Schaid DJ:
Alpha-1-antitrypsin phenotypes among patients with
intracranial aneurysms. J Neurosurg 84: 781784,
1996
13) Solander S, Ulhoa A, Vinuela F, Duckwiler GR,
Gobin YP, Martin NA, Frazee JG, Guglielmi G:
Endovascular treatment of multiple intracranial
aneurysms by using Guglielmi detachable coils. J
Neurosurg 90: 857864, 1999
14) Stanley JC, Gewertz BL, Bove EL, Sottiurai V, Fry
WJ: Arterial fibrodysplasia. Histopathologic charac-
ter and current etiologic concepts. Arch Surg 110:
561566, 1975
15) Suzuki K, Takatama M: [Histopathologic studies on
the etiology and rupture of cerebral aneurysm].
Myakkangaku 37: 355360, 1997 (Jpn, with Eng
abstract)
16) Thornton J, Debrun GM, Aletich VA, Bashir Q,
Charbel FT, Ausman J: Follow-up angiography of
intracranial aneurysms treated with endovascular
placement of Guglielmi detachable coils. Neurosur-
gery 50: 239250, 2002
17) Tonn JC, Hoffmann O, Hoffmann E, Schlake HP,
Sorensen N, Roosen K: De novo formation of in-
tracranial aneurysms: who is at risk? Neuroradiology
Neurol Med Chir (Tokyo) 42, September, 2002
 De Novo Cerebral Aneurysms
41: 674679, 1999
18) Tsutsumi K, Ueki K, Morita A, Usui M, Kirino T:
Risk of aneurysm recurrence in patients with clipped
cerebral aneurysms. Result of long term follow up an-
giography. Stroke 32: 11911194, 2001
19) Uchikawa K, Abe H, Ideguchi H, Kim I: [Follow-up
study after aneurysm surgery]. Surgery for Cerebral
Stroke 26: 171174, 1998 (Jpn)
20) Yamamoto K, Yoshida Y: [Pathology of subarachnoid
hemorrhage, with special reference to the morpho-
genesis of berry aneurysms of cerebral arteries and
mechanism of their rupture]. Myakkangaku 17:
183195, 1977 (Jpn)
Neurol Med Chir (Tokyo) 42, September, 2002
395
21) Yoshida S, Oda Y, Sato S, Matsumoto S, Yoo K,
Kobayashi S, Masunaga S, Imamura H, Hayase M:
[Recurrence of cerebral aneurysms in the long term
follow up after aneurysm surgery]. No Shinkei Geka
28: 10771082, 2000 (Jpn, with Eng abstract)
Address reprint requests to: K. Fukui, M.D., Department of
Neurosurgery, Nagoya Ekisaikai Hospital, 466
Shounencho, Nakagawaku, Nagoya 4548502,
Japan.
e-mail: k-fukuisannet.ne.jp.