Introduction
Morley and Barr classify cerebral aneurysms as giant when their largest diameter is
equal to or greater than 25 mm. The arbitrary limit of 2.5 cm distinguishes an aneurysm
group with clinical and pathological characteristics, natural history, and treatment,
which differ from those of small and medium aneurysms.[1]
[2]
[3]
[4]
The most common location is in the internal carotid artery (ICA), followed by the
vertebrobasilar system (VBS), middle cerebral artery (MCA), and most recently, the
anterior cerebral-anterior communicating artery (ACA-ACoA) complex.[1]
[2]
[4]
[5]
Manifestations include subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage
(ICH) and, particularly, signs and symptoms related to mass effect on the adjacent
neural structures. Seizures and cerebral ischemia occur with less frequency. The natural
history of giant cerebral aneurisms is very poor, since cases treated conservatively
evolve to death in a few years.[1]
[5]
[6]
[7]
[8]
The treatment of such aneurysms is one of the greatest neurosurgical challenges. The
difficulties involved are due to the size of the aneurysm, the presence of calcification
and thrombus, the wide neck, and the incorporation of the artery from which they originate.
Despite the increased difficulties in treatment and poor prognosis, they are potentially
curable lesions and some type of therapeutic intervention should always be considered.[9]
[10]
Natural History
The natural history of giant aneurysms is very poor, since they are associated with
high risk of bleeding, progressive neurological defects, and death, mainly a result
of bleeding, but also of the mass effect and/or cerebral ischemia. The condition presents
increased risk of SAH and higher mortality than small and medium aneurysms. Location
in the posterior circulation is an isolated factor for poor prognosis.[1]
[6]
[7]
[8]
[12]
[13]
Drake[32] reported mortality of 68% at 2 years and 85% at 5 years for untreated giant aneurysms
and the survivors showed severe neurological sequelae. According to the International
Study of Unruptured Intracranial Aneurysms (ISUIA),[11] the cumulative risk of bleeding is 40 to 50% at 5 years. Meningeal hemorrhage resulting
from a giant aneurysm leads to higher mortality and serious neurological sequelae
compared with smaller aneurysms ([Tables 1] and [2]).
Table 1
Natural history of unruptured aneurysms[11]
|
Anterior circulation aneurysms except ACoP
|
Annual risk of bleeding
|
|
7–12 mm
|
0.5%
|
|
13–24 mm
|
2.9%
|
|
≥ 25 mm
|
8.0%
|
Table 2
Natural history of unruptured aneurysms[11]
|
Posterior circulation aneurysms plus ACoP
|
Annual risk of bleeding
|
|
7–12 mm
|
2.9%
|
|
13–24 mm
|
3.7%
|
|
≥ 25 mm
|
10.0%
|
The exception to poor prognosis are giant aneurysms of the extradural ICA (petrous
and cavernous portion), which usually have a benign natural history. These can manifest
as multiple cranial nerves paresis (III, IV, and VI), ischemia secondary to migration
of intrasaccular thrombus, carotid cavernous fistula, and epistaxis.[1]
[4]
[13]
Treatment
The treatment should be performed in a neurosurgical center with experience in treating
patients with cerebral aneurysms, which can perform both microsurgery and endovascular
techniques. The treatment modalities are conservative, surgical, endovascular and
combined. Treatment management of giant aneurysms should take into account the risks
and benefits of each treatment option.[7]
[11]
There have not yet been any randomized clinical trials conducted on the topic. Current
literature data refer to large series in select centers. The decision process for
treating these lesions has been individualized; however, this should be discussed
within a multidisciplinary team.
Conservative Treatment ([Fig. 1])
Fig. 1 Conservative treatment. Patient, 65 years old, presenting hypertension and diabetes
with paresis of the III right cranial nerve. CT scan without (A) and with (B) contrast
show nodular lesion right temporal. Cerebral angiography in lateral (C) and 3D reconstruction
(D and E) confirmed giant aneurysm of the cavernous internal carotid artery. Patient
did not tolerate the balloon occlusion test (F).
It is mainly indicated for asymptomatic patients with an extradural giant aneurysm
of the intracavernous or petrous ICA. Patients with minor symptoms with a precarious
health status or of advanced age may also undergo monitoring. Patients with symptoms
of cerebral ischemia secondary to migration of an intrasaccular thrombus of a cavernous
aneurysm that are not candidates for other treatments may be administered an antiplatelet
agent.[11]
[18]
[19]
Surgical Treatment
Surgical treatment of giant aneurysms remains the optimal therapeutic choice in most
cases. The aim is to exclude the aneurysm from circulation, maintaining the patency
of the artery involved, eliminating the mass effects and conserving neurological functions.[4]
[18]
[20] Factors that can complicate surgery include: a wide neck, afferent and efferent
vessels encompassed by the aneurysm, the presence of intrasaccular thrombus, and calcifications
in the aneurysm neck and the source artery. Paraclinoid aneurysms and those located
in the posterior circulation represent a greater challenge.[9]
[17]
[18]
The patient's age and the morbidity of the treatment options factor into the decision
over treatment. In contrast to poor natural history, several surgical series have
reported good clinical outcomes in 58 to 84% of patients, with mortality rates ranging
from 14 to 22%.[13]
[17]
[18]
[20]
In the current series of 286 giant aneurysms, we observe a good clinical outcome (Glasgow
Outcome Scale; GOS 4 and 5) in 81.1% of cases and poor clinical outcome (GOS 1, 2,
and 3) in 18.9%. The results of the main surgical series (clipping, reconstruction
and bypass) are presented in [Table 3].
Table 3
Surgical morbidity and mortality of giant aneurysms in literature[4]
[17]
[18]
[21]
[22]
|
Literature results
|
Percentage
|
|
Good or excellent clinical outcome
|
58–84%
|
|
Mortality
|
14–22%
|
|
Rebleeding
|
0–3%
|
|
Retreatment
|
0–1%
|
Elderly patients with multiple comorbidities and aneurysms located in the posterior
circulation tend to present a worse clinical outcome. The use of adjuvant therapies,
such as temporary clipping, arresting the heart, deep hypothermia, and bypass, all
present increased specific risks that must be considered.[13]
[18]
[20]
[23]
Lawton et al[22] evaluated the results of surgical management in 141 intracranial giant aneurysms
operated between 1997 and 2010, on patients with a mean age of 54 years old. The majority
of patients presented symptoms of compression of the cranial nerves, while 23 patients
presented cerebral hemorrhage. One hundred aneurysms were located in the anterior
circulation, mainly in the ICA and the MCA, and 41 in the posterior circulation.
A direct approach with aneurysm neck clipping was the preferred primary treatment
strategy, comprising 66 (46.8%) of the cases. Alternatively, 72 (51.1%) patients underwent
an indirect approach. Bypass formed part of the treatment strategy in 54 (38.3%) aneurysms,
with the following distribution: high-flow bypass in 14 patients (25.9%); low-flow
bypass in 11 patients (20.4%); and 15 (27.8%) intracranial bypasses in situ and other
forms of bypass (reimplantation/reanastomosis) in 14 patients (25.9%). During follow-up
with control tests, 108 (76.6%) aneurysms were completely occluded, 14 (9.9%) had
minimal residual aneurysm neck, and 16 (11.3%) were incompletely occluded with aneurysm
reversal or flow reduction.[22]
We observed good clinical outcomes (GOS 4 and 5) in 114 (80.9%) patients. The mortality
rate was 12.8 and the neurological morbidity rate related to treatment was 9.2%. Factors
identified for poor prognosis were location in the posterior circulation, clinical
presentation with hemorrhage, and calcified aneurysms.[22]
Proximal and Distal Ligation of the Feeding Artery (Hunterian Ligation and Surgical
Trapping)
Dandy first proposed trapping, which consists of ligation of the feeding artery proximally
and distally to the aneurysm neck. This can be achieved using a surgical or endovascular
approach, the latter involves using detachable balloons or coils.[3]
[10]
[16]
The BTO should precede the applicaiton of such techniques. As described by Matas[10] in 1911, temporary occlusion of the internal carotid artery provides valuable information
for preoperative planning in cases of giant aneurysm. The parameters used are early
arterial filling difference, simultaneous capillary venous time, and collateral circulation
through the anterior communicating artery.[10]
[16]
[24] Induced hypotension is used to increase assay sensitivity, with reduction in blood
pressure (BP) to 20% of the baseline value or 20 mm Hg for 30 minutes, with serial
neurological examination assessment.[10]
[16]
[18]
[24]
When the patient shows tolerance for BTO, this means that they present good cerebrovascular
reserve and, therefore, should endure occlusion of the internal carotid artery with
low morbimortality. Surgical or endovascular occlusion of the internal carotid can
be performed without prior revascularization.[10]
[18]
[24]
According to Linskey et al,[25] ligation of the internal carotid without prior collateral flow studies results in
25% morbidity and 12% mortality; whereas, when ligation is performed after collateral
flow studies, morbidity is 4.7% and mortality is 0%. Therefore, when the patient shows
intolerance for BTO, a high-flow bypass is required prior to occlusion of the internal
carotid to guarantee cerebral perfusion.
Direct Clipping of the Aneurysm Neck or Reconstruction with Clips
According to some authors, the ideal treatment for giant aneurysms remains the direct
approach to the aneurysm using microsurgery. This is possible in ∼50–60% of cases.[4]
[18]
[26] Occlusion of the aneurysm neck using clips has several peculiarities. The success
of clipping a giant aneurysm depends on its morphology and anatomical complexity.
The aneurysm must have a well-defined neck ([Figs. 2], [3], and [4]). When direct neck clipping is inviable, the use of reconstruction techniques is
required to exclude the aneurysm from circulation ([Figs. 5] and [6]).[17]
[18]
[27]
Fig. 2 Direct approach to neck of the brain aneurysm. Patient with subarachnoid hemorrhage
diagnosed by CT scan without contrast (A). Cerebral angiography in lateral (B) and
anteroposterior (C) shows a giant aneurysm at the apex of the basilar artery narrow
neck. Performed microsurgical clipping with direct approach to the neck of the aneurysm
through fronto-orbitozygomatic craniotomy. Cerebral angiography control (D) showing
complete exclusion of the aneurysm with preservation of the posterior cerebral arteries.
Fig. 3 Direct approach to neck of the brain aneurysm. Giant aneurysm intracranial of the
internal carotid artery left evidenced by cerebral angiography AP (A) and lateral
(B). Intraoperative findings revealed compression of optic pathways (D) and early
proximal vascular control (E). Performed clipping of the aneurysmatic neck without
vascular stenosis (F). Control angiography (C) with complete exclusion of the aneurysm
from the circulation.
Fig. 4 Direct approach to neck brain aneurysm. Aneurysm of the middle cerebral artery (MCA)
left with lower projection evidenced by cerebral angiography AP (A) and lateral (B).
Intraoperative findings showing wide neck aneurysm of the MCA (C). Performed clipping
of the aneurysm without stenosis confirmed by angiography control in AP (D) and lateral
(E).
Fig. 5 Vascular reconstruction with multiple clips. CT scan (A) shows nodular lesion in
the right parasellar region. Cerebral angiography in AP (B) and lateral (C) show a
giant aneurysm of the intracranial internal carotid artery. Performed vascular reconstruction
with multiple fenestrated clips and control angiography (D) shows preservation of
vascular flow.
Fig. 6 Vascular reconstruction with multiple Clips. Intraoperative findings of vascular
reconstruction with multiple fenestrated clips show compression of the optic pathways
for aneurysm (A) and final aspect of the reconstruction of the internal carotid artery
(B).
The presence of arterial branches incorporated into the aneurysm body, a wide neck,
calcifications in the arterial wall, and/or aneurysm neck, all complicate the surgical
treatment. Calcifications can expel clips or prevent their closure. Due to these characteristics,
temporary clipping is used in most cases of giant aneurysm, allowing for dissection
of the neural structures and manipulation of the bottom of the aneurysm, thus, also
facilitating the application of clips. In giant partially thrombosed aneurysms, opening
of the aneurysm sac to empty the clots (thrombectomy) is required for a definitive
clipping of the neck.[4]
[17]
[18]
To minimize complications, neurosurgeons have relied on numerous “checking methods”
during the intraoperative period to ensure aneurysm exclusion and prevent vessel stenosis.
The most commonly used methods are intraoperative Doppler ultrasound and digital angiography.
More recently, the advent of video angiography with intravenous indocyanine green
has offered the neurosurgeon the same parameters albeit in a less invasive manner.[12]
[17]
[22]
[28]
Spagnuolo et al[13] reviewed 145 cases of giant aneurysm treated with direct surgical approach to the
aneurysm neck. Twenty-six patients presented cerebral hemorrhage. Patients with ruptured
aneurysms presented 15% mortality and 10% morbidity; in contrast, patients with unruptured
aneurysms presented 6.5% mortality and 15% morbidity. Complications mainly related
to occlusion/thrombosis of the affected vessel, with consequent cerebral ischemia,
hemorrhagic phenomena, and clinical complications.
Bypass with Proximal and Distal Occlusion
Yasargil,[11] in 1969, developed and introduced cerebral revascularization techniques into neurosurgery
practice. A bypass can be one of two types, according to the resulting blood flow:
high-flow or low-flow. The most commonly used type of revascularization in giant aneurysm
surgeries is a high-flow bypass between the cervical external carotid artery and one
of the M2 branches of the middle cerebral artery, with the interposition of a radial
artery or saphenous vein graft ([Fig. 7]). It is indicated when the patient shows intolerance for BTO and no other options
are viable.[26]
[29]
Fig. 7 Bypass and surgical trapping of the aneurysm. CT scan (A) with hemorrhage and mass
effect. Cerebral angiography in AP (B) and three-dimensional reconstruction (C) show
the internal carotid artery giant aneurysm (ICA) left with involvement of afferent
and efferent vessels. Performed bypass from the cervical external carotid artery to
M2 branch of the middle cerebral artery (D and E). Control angiography showing excluded
the aneurysm with good cerebral perfusion by shunt (F).
Jafar et al[21] analyzed the results of surgical treatment in 29 patients with giant aneurysms submitted
to extracranial-intracranial high-flow bypass with saphenous vein graft and immediate
occlusion of the vessel with the aneurysm. Follow-up at 62 months showed 6% neurological
morbidity and 3% mortality with 100% occlusion of the aneurysm from circulation. The
graft occlusion rate was 7% early and 0% late. The main complications related to ischemic
phenomena, such as choroidal artery infarction and perforating arteries. The authors
concluded that the use of extracranial-intracranial high-flow bypass with saphenous
vein graft followed by occlusion of the affected vessel is a safe, effective treatment
for giant aneurysms.[21]
Endovascular Treatment
The endovascular approach is a good treatment option for giant aneurysms, particularly
for unruptured aneurysms, spindle aneurysms, located in the posterior circulation,
and for elderly patients with multiple comorbidities. Despite the development of endovascular
technologies in recent years, they still present certain limitations, including incomplete
occlusion with high rates of recanalization, the need for retreatment, and occasional
post-treatment bleeding. This approach does not solve pseudo-tumor compressive effects
on the adjacent neural structures.[19]
[27]
Some factors intrinsic to giant aneurysms make them pathologies of difficult endovascular
treatment, such as a wide neck, with incorporation of the feeding artery, intraluminal
thrombosis, and the involvement of perforating.
Parkinson et al[19] analyzed the clinical results of the largest endovascular series for treatment of
giant aneurysms published since 1994, following the development of coils. They identified
316 patients submitted to endovascular treatment, in which 19% of cases manifested
cerebral hemorrhage. The average of complete aneurysm occlusion was 57% of cases,
with 7.7% mortality and 17.2% neurological morbidity during a mean clinical follow-up
of 17.6 months. The recanalization rate was 27% in 238 aneurysms followed for 12.4
months.[19]
When analyzing the exclusive use of coils as a treatment strategy, only 43% of cases
presented complete aneurysm occlusion, with 9% mortality and 24% major neurological
morbidity. The recanalization rate was 55% in 164 giant aneurysms followed. The exclusive
use of onyx, coil, and/or onyx stents showed similar results, making these viable
strategies for the safe, definitive treatment of giant aneurysms.[19]
Endovascular occlusion of the affected vessel with coil following BTO proved to be
safe and effective. In a review of 72 cases, Parkinson et al. verified 81% initial
occlusion and 1% recanalization.[19] Mortality rate was 7% of neurological morbidity followed for 14 months.[19]
Jahromi et al[15] retrospectively analyzed the clinical and angiographic outcomes following endovascular
treatment of 39 giant aneurysms. Ten patients presented ruptured aneurysms. Treatment
with stents and coils was used in 25 aneurysms. An average of 1.9 sessions was required
to treat each aneurysm, with 95% angiographic occlusion of aneurysms and 75% patency
of the affected vessel. The 30-day mortality was 8%, with 20% permanent neurological
morbidity.
Flow diverter stents are designed to induce redirection of blood flow near the aneurysm
neck, preserving it in the affected vessel and its branches. They can be a good treatment
option for basilar, petro-cavernous, and paraclinoid aneurysms, for which surgical
options present particularly high morbimortality. Given the need for dual-antiplatelet
therapy, the use of flow diverters is not recommended when the aneurysm is ruptured
due to the higher incidence of hemorrhage and worse clinical outcome.[23]
[30]
The Pipeline for Uncoilable or Failed Aneurysms (PUFs) trial[20] evaluated the safety and efficacy of the pipeline embolization device (PED) in the
treatment of large and giant aneurysms with a wide neck. The primary outcome was death
or ipsilateral stroke within 180 days. The PED was used prospectively in 108 patients
in 10 centers on 22 (20.4%) giant aneurysms and 85 (78.7%) large aneurysms. The complete
occlusion rate was 73.6% at 180 days and 86.8% at one year. The primary outcome for
six (5.6%) patients was death or ischemic stroke, while 44 patients presented serious
adverse effects, including cerebral hemorrhage (4.7%), amaurosis fugax (4.7%), headache
(4.7%), non-neurological bleeding (4%), ischemic stroke (3.7%), carotid cavernous
fistula (1.9%), cardiac arrhythmia (2.8%), and carotid occlusion (0.9%).[20]
