Neurochirurgie 63 (2017) 6–12

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Original article

Growth of giant intracranial aneurysms: An aneurysmal wall
disorder?
F.-X. Ferracci a,∗ , V. Gilard b , H. Cebula d , N. Magne b , J.-P. Lejeune c , O. Langlois a , F. Proust d
a

Department of Neurosurgery, Rouen University Hospital, 1, rue de Germont, 76031 Rouen cedex, France
Department of Neuroradiology, Rouen University Hospital, 76000 Rouen, France
Department of Neurosurgery, Lille University Hospital, 59000 Lille, France
d
Department of Neurosurgery, Strasbourg University Hospital, 67000 Strasbourg, France
b
c

a r t i c l e

i n f o

Article history:
Received 29 March 2015
Received in revised form
13 December 2016
Accepted 1st January 2017
Available online 8 March 2017
Keywords:
Giant intracranial aneurysm
Vasa vasorum
Aneurysmal wall

a b s t r a c t
The enlargement of giant intracranial aneurysms (IA) can be observed in 30 % of cases resulting in a
neurological deﬁcit and epilepsy due to its mass effect. This growth process could be due to a morphological disorder of the IA wall. The authors report on 2 cases of giant IA growth responsible for intracranial
hypertension. The treatment of these giant IA required a microsurgical excision combined with a series of
cerebral revascularization procedures. The role of vasa vasorum on the inﬂammatory granuloma outside
the vessel, which induced the enlargement, is discussed. These cases illustrate the abluminal vasculopathy
as the main involvement of this unfavourable natural history.
© 2017 Elsevier Masson SAS. All rights reserved.

1. Introduction

2. Case report

The giant intracranial aneurysm (IA), representing 2–4 % of all
aneurysms [1–5], are unstable dynamic entities responsible for
a morbidity and mortality rate of approximately 65 % at 2 years
[6–10]. In addition to the aneurysm ﬁssuration which occurs in
40 to 60 % of patients at 5 years [9,10], the aneurysm enlargement has been observed in 30 % of patients over a period of
16 days–5 years resulting in neurological deﬁcit and epilepsy due
to its mass effect [11–13]. This growth event probably occurs in
a particular subgroup of giant IA which are the partially thrombosed aneurysms. These aneurysms are differentiated from those
that are completely perfused and more prone to ﬁssuration [14].
This process of growth could be due to a morphological disorder of the IA wall [15]. The aim of our study was to report
2 cases of giant IA, which illustrated the process of growth from
the wall sac and discuss the pathology involved reported in the
literature.

2.1. Case #1

∗ Corresponding author.
E-mail address: francois-xavier.ferracci@neurochirurgie.fr (F.-X. Ferracci).
http://dx.doi.org/10.1016/j.neuchi.2017.01.001
0028-3770/© 2017 Elsevier Masson SAS. All rights reserved.

2.1.1. Initial management
A 20-year-old male patient was admitted in emergency for
drug-resistant headaches. The patient presented with intensive
headaches, nausea, and a memory disorder reported by his mother.
At examination, we observed a bilateral papillary edema on the
fundus without any decrease in visual acuity, a mini mental scale
(MMS) of 23/30 and no sensitive or motor deﬁcit. His previous medical history was characterized in 2009 by the diagnosis on MRI of
a fusiform dilatation on the horizontal (M1) segment of the right
middle cerebral artery (MCA) combined to smoking as a vascular
risk factor. The neurovascular team proposed an annual radiological follow-up of this arterial fusiform dilatation of 7 mm and an end
to smoking addiction due to the beneﬁt-risk balance of treatment.
The patient was lost to follow-up in 2012 (Fig. 1).
At the admission, the CT scan with no contrast agent revealed
a 30 mm nodular lesion occupying all the temporal fossa, opening the right sylvian ﬁssure and responsible for an hydrocephalus
with mass effect on the third ventricle. The brain magnetic resonance imaging (MRI) suggested the diagnosis of serpentine giant
aneurysm on MCA due to a large partial thrombosis (Fig. 2). The
cerebral angiography conﬁrmed a serpentine channel on the superior aspect of the aneurysm located on the right side of the MCA.
The occlusion test balloon of the right internal carotid artery (ICA)

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Fig. 1. a: axial time of ﬂight (TOF) image shows the tumoral and circulating part of the aneurysm, measuring 30 × 21 × 17 mm, justifying the conservative treatment; b:
frontal rebuilding views of TOF revealed the circulating part of the dysplasia concerning the M1 segment of the right MCA. Segment M2 is free from the dysplasia; c: three
years later, coronal gadolinium enhancement T1-weighted MRI showed bulky thrombosed part, and permeable channel at the upper part of the aneurysm are found, like
in the Digital Subtraction Angiography (DSA); d: it was measured to 61 × 30 × 39 mm. The important midline shift showed on this MRI, because of the volumetric growing
(+370 %), make chosen quick surgical management.

was negative due to the absence of perfusion on the distal territory
of the MCA via the anterior communicating artery.
Prior to the optimal management of this complex aneurysm,
the papillary edema required a ventriculo-peritoneal shunt (VPS)
implantation in emergency. A visual deterioration, due to the persisting mass effect, was observed despite the complete resolution of
a papillary edema: binocular diplopia related to third cranial nerve
paralysis and visual acuity of the left eye which decreased to 2/10.
After discussion with several neurovascular teams, we proposed
a procedure of cerebral revascularization permitting a resolution of
mass effect by removal of the giant aneurysm.

2.1.2. Operative report
Under general anesthesia, installation of an extracorporeal circulation (ECC) system was performed. The arc shape cutaneous
incision for a fronto-pterional access was carried-out in front of the
superﬁcial temporal artery (STA), previously identiﬁed by Doppler
ultrasound. Then ECC was started under hypo-coagulation. The
proximal part of the fusiform aneurysm was disconnected from
the supraclinoid portion of the ICA and clipped. After performing
an end-to-side anastomosis between the STA and the M2 segment of the MCA, the intra-aneurysmal thrombosis was removed in
order to resolve the mass effect. Intraoperative video and indocyanine angiography conﬁrmed bypass patency. The histopathological
report conﬁrmed inﬂammatory reaction in the aneurysmal wall

with large atherosclerosis and thrombosis. Moreover, neoangiogenesis and intra-mural bleeding occurred.
2.1.3. Outcome
The immediate postoperative CT angiography conﬁrmed the
good permeability of the STA-MCA bypass. A ventricular dilation
required drainage by external ventricular derivation (EVD). The
patient awoke with an incomplete left hemiplegia, which gradually
improved. One month after the surgery, the patient presented with
a left hemiparesis (4/5), and a left hand deﬁcit thin movement and
diplopia. At 6 months, the patient was able to walk, with disability
to run. We also found a paresis of left upper limb and left central
facial paralysis grade I, with no diplopia. The MMS was evaluated
at 28/30.
Postoperative MRI, revealed a right hemispherical hypoperfusion: right side cerebral blood ﬂow was estimated at 19.83 ml/sec
for the left side at 49.2 ml/sec and cerebral blood volume of 2.4 ml
on the right for 3.4 ml on the left. At 6th months, the MRI showed
no cortical ischemia. The STA-MCA anastomosis diameter was measured at 1;8 mm.
2.2. Case #2
2.2.1. Initial management
A 57-year-old male patient consulted for fortuitous diagnosis of
giant aneurysm located at the major bifurcation of the right MCA

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F.-X. Ferracci et al. / Neurochirurgie 63 (2017) 6–12

Fig. 2. a: T2-weighted FLAIR MR image postoperative revealed no cerebral ischemia in the right MCA territory; b: 3D reconstruction from TOF sequence showed perfectly
the right cerebral vascularization by the external carotid artery; c: the STA-MCA anastomosis diameter was measured to 1,8 mm in proximal and 2,1 mm in distal.

revealed by MRI (Fig. 3a). His previous medical history was characterized by chronic limb arteriopathy and a vascular risk factor
of arterial hypertension, dyslipidemia and smoking. The cerebral
angiography conﬁrmed the partial thrombosis of a giant aneurysm
(Fig. 3b), only the upper part of the aneurysm circulated. After
prescription of antiplatelet agent, the National College of Vascular Neurosurgeons proposed surgical treatment using a cerebral
revascularization procedure.
Two months later, the patient was admitted in emergency
for sudden and severe headaches. The clinical examination
revealed a memory disorder, executive and linguistic difﬁculties
(MMS = 19/30). The MRI showed a major (130 %) size × aneurysm
diameter increase due to a dissecting hematoma in the sac wall
(Fig. 4) responsible for a large mass effect. The CT angiography conﬁrmed the size increase due to a dissecting hematoma in the sac
wall from the thrombosis part of the aneurysmal sac, the bifurcation
remained circulating.
The rapid neurological deterioration due to the intracranial
hypertension required an early neurosurgical solution.

the complete removal of the aneurysmal sac was performed. The
histopathological report conﬁrmed the inﬂammatory reaction in
aneurysmal wall with inﬂammatory granuloma and intrasaccular
thrombosis. Moreover, neoangiogenesis with intra-mural bleeding
was present.
2.2.3. Outcome
The immediate postoperative CT angiography conﬁrmed the
good permeability of the MCA-MCA bypass. In the postoperative
period, the patient awoke with an incomplete left hemiplegia, associated with a left hemianopsia, and left hemispatial neglect. Two
weeks after the surgery, the left hemiparesis had disappeared, but
hemianopsia and hemispatial neglect persisted in association with
a temporo-spatial disorientation. At discharge, the patient was able
to walk, and presented a MMS evaluated at 17/30.
At 6 months, the MRI showed ischemia in the territory of the
temporal branch of the right MCA, and the MMS was evaluated at
26/30.
3. Discussion

2.2.2. Surgery report
Under general anesthesia, an arc shape incision was performed
for a fronto-pterional access, in front of the STA, individualized by
Doppler ultrasound. After a craniotomy, the mass effect resulted in
a primary reduction of the giant aneurysm from the non-circulating
part of the aneurysm. This reduction permitted the dissection of
the MCA bifurcation, but the endocranial atherosclerosis required
to sacriﬁce the major MCA bifurcation. At ﬁrst, an end-to-end anastomosis was performed between M1 and temporal artery (M2) and
an end-to-side between the frontal artery (M2) and M1. Intraoperative video indocyanine angiography conﬁrmed bypass patency and

In our 2 cases, the intracranial hypertension due to this growing
giant IA was the major argument to propose these complex strategies, of microsurgical resection combined with various bypass
techniques, with recovery of functional autonomy at 6 months.
Our cases illustrated by serial neuroimaging the instability of giant
aneurysms, which may even occur after some weeks as in our case
#2. In the absence of the histopathological investigation of both
reported aneurysmal cases, it is not possible to argument one mechanism but only serves to illustrate growth and stimulate reader’s
curiosity.

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Fig. 3. T1-weighted MRI with gadolinium enhancement in sagittal (a) and coronal (b) views showed a giant aneurysm partially thrombosed, measuring approximately
37 × 34 mm with a circulating part of 15 × 16 mm. At its posterior portion, was showed a high signal intensity on T1-weighted who traduced a sub-acute hemorrhagic event
due to neovascularization of the aneurysm’s wall. DSA (c, d) conﬁrmed this aneurysm of the right middle cerebral artery, measuring 16 × 18 mm with a neck measured to
5 mm.

Fig. 4. Fusion between, the two month later images, T1-weighted MRI and CT angiography. The colored part corresponded to the circulating portion of this aneurysm. On
axial reconstruction (a, b), the arrow showed the wall’s aneurysm. The recent bleeding was inside this wall at the peripheral part, corresponding to the T1 high signal intensity
( ). Coronal view (c) showed the important mass effect on the midline, due to the growing, with a deviation of 11 mm towards the left.

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The growth of giant IA, classically considered as a pseudo-tumor,
could be the result of the interplay between luminal and abluminal factors applied on the IA wall [14,15]. Based on our literature
analysis, we were able to better understand the parameters which
determined this malicious natural history.
3.1. Luminal vasculopathy: shear stress thrombus formation
hypothesis
The growing IA process is a complex association of mechanisms
depending on hemodynamic conditions. The most representative
hemodynamic parameter is the wall shear stress (WSS), deﬁned
as the frictional force exerted by the blood ﬂowing tangentially on
the vessel lumen [16–18]. WSS is a mechanical trigger transducing
to the vessel wall into biological signals (mediators of remodeling)
reported by Chalouhi et al. [19] as endothelial dysfunction related to
hemodynamic stress. It is determined by its vulnerability, the initial
outpouching, the IA growth and its geometric outcome [16,20,21].
Taking into account the intraoperative observation of unruptured IA, the giant IA may be considered as a type II phenotype
[22,23]. These types of aneurysms are characterized by their large
size with an irregular surface on which yellowish plaques of
atherosclerosis obstruct the intra-aneurysmal blood ﬂow. The histologic analysis of this type II phenotype IA conﬁrmed a low rate of
thin-walled regions with high rate of thick walls with atherosclerotic changes and inﬂammatory cells [24–26]. Moreover, recent
studies using image-based computational ﬂuid dynamics (CFD)
have shown the confusing role of low or high WSS involved in the
development of IA. Interestingly, Meng et al. hypothesized that the
WSS-low-driven could be responsible for type II IA [21,27].
This inﬂammatory-cell-mediated pathway could be considered
as a repair or remodeling process of the IA wall determining the
histological characteristics of unruptured IA (such as inﬂammatory
inﬁltration, smooth muscle cell migration to intima and thrombus organization [26]). This atherosclerotic process inside the IA
wall subsequently determined the formation of luminal thrombus
related to the exposition of thrombogenic materiel from atherosclerotic plaque to the blood stream [28–30]. This intramural thrombus,
initially atherosclerotic, might become growing by combination of
inﬂammatory process to recurrent bleeding secondary to neoangiogenesis in type II IA wall.
The growing geometry of giant aneurysm was due to abluminal process determining thrombus expansion mediated by
inﬂammatory processes. The 5-lipoxygenase (5-LO) pathway of
arachidonic acid metabolism, leading to the biosynthesis of the
potent lipid inﬂammatory mediators leukotrienes, would involve
in the neoangiogenesis process. Moreover, the Krüpper-like zingﬁnger transcription factor 5 (KLF5) was highly expressed in large
and giant unruptured aneurysms [31].
3.2. Abluminal vasculopathy: intramural dissection hypothesis
Some authors have reported their detailed observations of this
IA growth process. Kaneko et al. [13], describing a serial neuroimaging of a distal anterior cerebral artery IA becoming giant
in an 82 year-old patient, focused their observation on a lobulus
growth appearing as high intensity on T1- and low intensity on
T2-weighted images at its periphery. This small lesion was considered to indicate a new hemorrhage 2 months after the diagnosis
of aneurysm growth. Katayama et al. [32], reported a case of completely thrombosed IA becoming giant despite the absence of patent
arterial lumen. Its onion-skin appearance on MRI was interpreted
as various stages of hemoglobin degradation [33,34]. The layers
of fresh thrombus are diagnosed within the periphery of giant
aneurysm. In contrast, older thrombus could be detected in the
central parts [33,35,36]. In our case #2, the growing process was

located on the periphery (temporal pole of IA) away from the circulating blood ﬂow component.
This “onion-skin” organization of the intramural thrombus
argues in favor of the hypothesis of intramural recurrent hemorrhage rather than intraluminal accumulation of thrombotic
material. The apposition of new layers of thrombus in periphery of
the giant IA could involve the neoangiogenesis developed within
the aneurysmal wall. As proposed by Lasjaunias et al. [37], the
growth of a giant IA must be understood as an abluminal process from the outside of the lesion. Curiously, our 2 cases differed
morphologically: serpentine IA in contrast to the nodular could be
determined by the initial location and shape of the atherosclerotic
thrombus. The IA neck size combined to the blood ﬂow axis of the
parent vessel could be the determining factors. For example, a sessile IA could determine an extensive intramural thrombus by the
shear ﬂow, resulting in the constitution of serpentine giant IA.
Moreover, the intramural recurrent hemorrhage could be
related to dissection process driven by the shear stress on the edge
of the aneurysm neck or at the vessel dissection point. Nevertheless, this place of least resistance may be far from the far from the
origin of bleed.
3.3. Vasa vasorum involving
This intramural recurrent hemorrhage of growing IA could be
related to the pathological wall involving the vasa vasorum [14,15].
The vasa vasorum constitutes an arterial network of 20–30 ␮m
within the adventitial layers supplying nutriments and oxygen
to the media and adventitia [38]. In contrast to the extracranial arteries, the intracranial vasa vasorum does not exist at the
birth. However, in some autopsy series of adults, specimens were
observed at the proximal portion of the ICA and vertebral artery
just in contact with the dural penetration [39–42]. There is evidence that the vasa vasorum develops in response to a pathological
process such as atherosclerosis [43] or large aneurysm [39,44–47].
Different mechanisms require the involvement of vasa vasorum
in the growth of giant aneurysm. The repeat bleeding from vasa
vasorum deposits outer layers of intramural hematoma [37]. The
inﬂammatory process on the aneurysmal wall was induced by vasa
vasorum and release of vascular growth factors [48]. This process
could be involved into some associated perianeurysmal edema
related to the loss of brain blood barrier in contact to the vasa
vasorum [49].
Moreover, this inﬂammation induces a vicious circle of wall
neoangiogenesis from the vasa vasorum like within the neomembrane of the chronic subdural hematoma. The complete or partial
occlusion of vasa vasorum may create some points of weakness
in the vessel wall [50]. This process was responsible for necrosis or intramural ﬁssuration. CT scan and the MRI could be able
to identify the density increasing of neoangiogenesis into the
wall of this growing aneurysm. From report of 3 cases of giant
aneurysm analyzed by CT scan, Byrd et al. [51] speculated that the
adventitial inhomogeneous enhancement represented wall neoangiogenesis. Iihara et al. [47], reporting an anatomo-clinic case of
thrombosed giant vertebral aneurysm, revealed during the intraoperative observation a plethora of vasa vasorum from the dura mater
appearing as a hyperintense rim on Gd-enhanced T1 -weighted
images. Nakatomi et al. [46], from 8 cases of serpentine aneurysms
with anatomo-imaging analysis, showed the correlation of the
contrast-enhancement of the inside of the aneurysmal wall on MRI
and the intimal neoangiogenesis on histological examination. In
our case #1, we observed a rim enhancement on the aneurysmal
wall on the preoperative MRI. The identiﬁcation of focal aneurysm
wall enhancement on MRI could be considered as the sign of
vasa vasorum formation. The sequences on 3-T MR Imaging to
explore these intracranial vessel walls would be a two-dimensional

F.-X. Ferracci et al. / Neurochirurgie 63 (2017) 6–12

T1 -weighted ﬂuid-attenuated inversion recovery (FLAIR), a highresolution three-dimensional isotropic turbo spin-echo acquisition
(VISTA) and a Gd-enhancement T1 -weighted [38].
3.4. Clinical implications
In contrast to the general assumption, the inﬂammatory process
is crucial for the development of this giant aneurysm. Recent study
underlined the interest of anti-inﬂammatory agents in this indication [52,53]. Moreover, the modiﬁcations of hemodynamic shear
stress by ﬂow diversion could be an interesting way to develop
in order to stop the inﬂammatory process. The use of a pipeline
embolization device could determine the protection against the
inﬂammatory vasculopathy [54,55].
4. Conclusion
The growing of giant aneurysm is related to an inﬂammatory
granuloma involving the development of vasa vasorum network.
This process may occur in some weeks, responsible for intracranial
hypertension, requiring the proposition of complex management.
In giant IA, the combination of luminal and abluminal vasculopathy
is the probable substratum of its growth.
Financial support
None.
Disclosure of interest
The authors declare that they have no competing interest.
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