Open Access Original

Article DOI: 10.7759/cureus.8290

Endovascular Treatment of Giant

Intracranial Aneurysms
Italo Linfante 1 , Vincenzo Andreone 2 , Natalia Ravelo 3 , Amy K. Starosciak 4 , Bilal Arif 3 ,
Hussain Shallwani 5 , Peter Tze Man Kan 6 , Michael W. McDermott 7 , Guilherme Dabus 8

1. Neurology, Miami Cardiac & Vascular Institute/Miami Neuroscience Institute, Baptist Health South
Florida, Miami, USA 2. Neurology & Stroke Unit, Ospedale Antonio Cardarelli, Napoli, ITA 3.
Neuroscience, Herbert Wertheim College of Medicine, Florida International University, Miami, USA 4.
Neurology, Miami Neuroscience Institute, Baptist Health South Florida, Miami, USA 5. Neurosurgery,
University at Buffalo SUNY, Buffalo, USA 6. Neurosurgery, Baylor College of Medicine, Houston, USA 7.
Neurological Surgery, University of California San Francisco, San Francisco, USA 8. Radiology, Miami
Cardiac & Vascular Institute/Miami Neuroscience Institute, Miami, USA

Corresponding author: Italo Linfante, linfante.italo@gmail.com

Abstract
Objective
Giant intracranial aneurysms (GIAs) are associated with a high risk of rupture and have a high
mortality rate when they rupture (65-100%). The traditional microsurgical approach to secure
these lesions is challenging, and as such endovascular embolization has been increasingly
selected as a treatment option.

Methods
We performed a retrospective analysis of consecutive patients with ruptured and unruptured
GIAs at three medical centers from October 2008 to April 2016. Clinical follow-up and digital
subtraction angiography were conducted at six months post-treatment. Chi-square analysis was
used to determine differences in outcomes between anterior and posterior circulation
aneurysms and if a pipeline embolization device (PED) provided favorable outcomes in
unruptured GIAs.

Results
A total of 45 consecutive patients (mean/median age = 57/59; range: 16-82 years) were
included. The mean/median aneurysm size was 29.9/28.3 mm (range: 25-50 mm). Eight (18%)
patients presented with aneurysmal subarachnoid hemorrhage and 37 (82%) with unruptured
GIAs. Twenty-eight (62%) were treated with a PED: 11 (24.4%) with one PED, 1 (2.2%) with PED
+ coils, 11 (24.4%) with more than one PED, and 5 (13.5%) with multiple PED + coils. The overall
Received 04/21/2020
mortality rate was 3/45 (6.7%). No deaths were procedure-related. Five (11.1%) patients
Review began 05/06/2020
Review ended 05/15/2020 experienced ischemic stroke but only 2 had a 90-day modified Rankin Scale (mRS) score of ≥3.
Published 05/26/2020 Of 33 patients available for six-month angiography, Raymond scale (RS) scores were 1, 2, and 3
for 23/45 (70%), 7/45 (20.9%), and 3/45 (9.1%), respectively. Chi-square test demonstrated that
© Copyright 2020
Linfante et al. This is an open access overall, anterior circulation GIAs had better clinical (mRS score) and radiographic (RS score)
article distributed under the terms of outcomes than posterior GIAs. PED alone provided similar clinical mRS outcomes but had a
the Creative Commons Attribution higher rate of complete occlusion at six months compared with PED + coils and coils alone in
License CC-BY 4.0., which permits
unruptured GIAs (p < 0.05).
unrestricted use, distribution, and
reproduction in any medium, provided
the original author and source are
Conclusions
credited.
Endovascular embolization using PED or PED + coils appears to be a moderately safe and

How to cite this article

Linfante I, Andreone V, Ravelo N, et al. (May 26, 2020) Endovascular Treatment of Giant Intracranial
Aneurysms. Cureus 12(5): e8290. DOI 10.7759/cureus.8290
 effective treatment option for patients with GIAs.

Categories: Neurology, Neurosurgery

Keywords: coiling, endovascular, giant intracranial aneurysm, pipeline embolization device

Introduction
Cerebral aneurysms are defined as giant when their diameter is ≥25 mm [1-6]. They represent
<5% of all intracranial aneurysms, making them rare among all aneurysms [3-5,7]. The natural
history of giant intracranial aneurysms (GIAs) is characterized by progressive growth,
thrombosis, and rupture [1,3,5,6,8,9]. Rarely, GIAs present with hemorrhage; therefore, many
are revealed by neuroimaging performed for headache, seizure, stroke, or progressive focal
deficit [7]. The risk of rupture (RR) of untreated, unruptured GIAs is 8-10% per year, with a
mortality of 65-100% at one to five years follow-up [10,11]. For aneurysms of any size, the RR is
increased for posterior circulation aneurysms compared with anterior circulation aneurysms;
therefore, it is likely that posterior circulation GIAs have a higher RR than anterior circulation
GIAs [12]. With these statistics in mind, surgical and endovascular management of patients
harboring these lesions is the most appropriate option in most cases.

The treatment of ruptured or unruptured GIAs is particularly challenging, with mortality rates
in microsurgical clipping of both ruptured and unruptured GIAs reported to be 6-22% [6,10]. An
endovascular approach including parent artery occlusion, coil embolization, stent-coil
embolization, remodeling technique, and covered stent has been used more recently as an
emerging technique to treat these lesions [6].

Recently, high rates of complete aneurysm occlusion have been reported in the treatment of
giant aneurysms with the use of endoluminal flow diverters. The Pipeline Embolization Device
(PED; Medtronic, Minneapolis, MN, USA) received FDA approval in 2011 (PMA P100018) for the
treatment of large and giant wide neck aneurysms of the internal carotid artery. In the
International Retrospective Study of the Pipeline Embolization Device (IntrePED), 66
aneurysms (7.3%) were giant, whereas in the Pipeline for Uncoilable or Failed Aneurysms
(PUFS) study, 22 (20.4%) were larger than 25 mm in maximum dimension [2,13]. We present
here our recent three-center experience with the endovascular treatment of patients with giant
aneurysms using PED, coil, or onyx embolization.

Materials And Methods

The current analysis was approved by Institutional Review Boards of three medical centers:
Miami Cardiac & Vascular Institute (MCVI) in Florida, University at Buffalo (UB) in New York,
and Baylor College of Medicine (BCM) in Texas. Informed consent for the procedure was
obtained from each patient. The patients included in this analysis were obtained from a
retrospective review of our database of consecutive ruptured and unruptured GIAs treated
endovascularly at our three centers between October 2008 and April 2016.

The decision on the best treatment approach for each was discussed between the
cerebrovascular neurosurgical attending and interventional neuroradiology attending. All
patients underwent a conventional digital subtraction angiography (DSA) including three-
dimensional reconstructed images at the time of admission. Treatment of the aneurysm was
based on each operator’s preference, including the timing of external ventricular drain
placement, number of PEDs used, coil selection, administration and dose of anti-platelet agents
such as aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors, and perioperative
management of the patients. The timing and modality of follow-up postoperative imaging were
also dependent on the operator’s preference and the clinical status of the patient. However, all

2020 Linfante et al. Cureus 12(5): e8290. DOI 10.7759/cureus.8290 2 of 15

 patients underwent a DSA at six months post-treatment.

We collected basic patient demographics, aneurysm size, location, the number and sizes of
PEDs used, use of coiling, 90-day modified Rankin Scale (mRS) score, and follow-up imaging
data (Raymond Scale, RS). Position and immediate angiographic result were recorded with
conventional DSA imaging with or without XperCT (Philips Healthcare, Best, the Netherlands)
and Low Contrast Imaging (LCI, Canon Medical Systems,Tochigi, Japan). Patients were admitted
to the intensive care unit (ICU) following treatment for further observation and management.

The primary clinical outcome was the 90-day mRS score and the primary radiographic outcome
was the six-month RS score. Rate of follow-up for clinical and radiographic outcomes and the
outcomes themselves were compared for anterior and posterior circulation aneurysms. Because
of the nature of the individualized therapy provided for each case, there was a relatively small
sample size in treatment types, such as PED alone versus PED + coils in anterior and posterior
or ruptured and unruptured aneurysms. Therefore, in unruptured aneurysms only, chi-square
analysis was used to determine if proportions of good clinical (mRS score: 0-2 vs. 3-6) and good
radiographic (RS score: 1 vs. 2-3) outcomes were statistically significantly different between
those treated with PED only, PED + coils, and coils alone.

Results
Data were collected on a series of 45 consecutive patients with a diagnosis of ruptured or
unruptured giant aneurysm who were treated endovascularly from October 2008 to April 2016
(Table 1). Of the 45 patients, 15 were treated at MCVI, 21 at UB, and 9 at BCM. The study
population consisted of 30 (66.7%) females and 15 (33.3%) males, with a mean age of 57 years
(median: 59 years; range: 16-82 years).

mRS 90-day Six-

Size Ruptured H&H
Case Age Location Initial treatment Complication score pre- mRS Rescue therapy month
(mm) unruptured scale
procedure score RS

1 80s L SCA 32 Unruptured n/a Onyx embolization None 1 1 None 1

2 50s L ICA 28 Ruptured III Coiling None 0 0 None 1

Secondary ischemic Flow diverter for residual

3 60s L MCA 25.3 Ruptured I Coiling 0 0 1
stroke aneurysm lumen

4 50s L ICA 25 Unruptured n/a PED None 0 0 None 1

5 60s L MCA 26 Unruptured n/a PED Mild vasospasm 0 0 None 1

6 60s R VA 35 Unruptured n/a Coiling None 4 6 None n/a

7 60s L ICA 25.2 Unruptured n/a PED None 1 0 None 1

8 70s L ICA 40 Unruptured n/a PED None 2 2 None 1

9 60s R ICA 46 Unruptured n/a PED None 1 1 None 1

Endovascular treatment for

10 50s L ICA 26 Unruptured n/a Coiling None 5 2 1
residual aneurysm lumen

11 Teen L ICA 28.1 Unruptured n/a PED None 0 1 None 1

Hemicraniectomy for

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 hydrocephalus, IA
Secondary ischemic
12 40s R MCA 25 Ruptured III Coiling 4 1 nicardipine and angioplasty 1
stroke
of the supraclinoid ICA for

vasospasm

13 70s L ICA 25 Unruptured n/a Coiling None 0 0 None 1

14 20s R MCA 26 Ruptured IV Coiling Intracranial bleeding 5 6 None n/a

15 60s R ICA 32 Unruptured n/a PED None 1 0 None 1

16 60s L ICA 28 Unruptured n/a PED None 1 0 None n/a

Evacuation of hematoma

Femoral artery from femoral artery

17 50s R ICA 50 Unruptured n/a PED (x2) and coiling 0 0 n/a
pseudo-aneurysm pseudoaneurysm through

drain

Two additional PEDs for

18 50s R ICA 27 Unruptured n/a PED None 1 1 3b
residual aneurysm

Integrilin (for TIA),

Intraoperative TIA; craniectomy, and clot

19 60s R ICA 26 Unruptured n/a PED (x2) post-operative SAH 2 4 evacuation (for SAH and 1

and IPH IPH); two additional PEDs

for residual aneurysm

20 50s R ICA 31 Unruptured n/a PED None 1 0 None 1

6 (not

21 50s L ICA 35.8 Unruptured n/a PED (x3) None 1 procedure None n/a

related)

22 60s R ICA 28.5 Unruptured n/a PED (x2) and coiling None 1 n/a None n/a

Intraoperative

23 40s BA 37.1 Unruptured n/a PED (x3) and coiling perforator occlusion 1 n/a IA Integrilin n/a

(causing TIA)

Integrilin, heparin, additional

Complete PED
doses of ASA and
occlusion, and right
24 30s R MCA 25.3 Unruptured n/a PED (x2) and coiling 0 1 clopidogrel, attempted 1
lentiform and caudate
aspiration thrombectomy of
nucleus infarct
MCA embolic material

25 50s R ICA 30 Unruptured n/a PED (x2) None 1 0 None 1

Multiple endovascular

26 40s R ICA 27.7 Ruptured III Stent-assisted coiling None 3 n/a treatments for residual n/a

aneurysm

Incomplete coverage Multiple PED deployment

27 60s L ICA 28.9 Unruptured n/a PED 0 n/a n/a
of aneurysm by PED (delayed)

Mild cavernous sinus

28 60s R ICA 27.4 Unruptured n/a PED (x3) 1 1 Prednisone 1
syndrome

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 Thrombosis of small

perforators, Anticoagulation and IV

Multiple stents for
29 30s BA 36 Unruptured n/a subsequent 1 n/a Integrilin for perforator n/a
vessel reconstruction
reperfusion thrombosis

hemorrhage

IA verapamil for bilateral

Bilateral ICA
Balloon-assisted ICA vasospasm; multiple
30 50s L ICA 25 Ruptured IV vasospasm (unrelated 5 n/a n/a
coiling endovascular treatments for
to procedure)
residual aneurysm

Aneurysm neck

coiling and parent

Right CN VII
31 40s R ICA 30 Unruptured n/a vessel sacrifice 1 n/a None n/a
(peripheral) plegia
(coiling and n-BMA

embolization)

Balloon angioplasty for L

ICA and MCA vasospasm;

L ICA and MCA
IA verapamil for L ICA;
32 40s R PCA 26.3 Unruptured n/a Stent-assisted coiling vasospasm and 1 1 2
multiple endovascular
ischemic stroke
treatments for residual

aneurysm

IV Integrilin (for ischemic

Secondary ischemic stroke); multiple

33 40s R ICA 26.4 Ruptured IV Coiling 5 3 3b
stroke endovascular treatments for

residual aneurysm

Multiple endovascular
Balloon-assisted
34 60s R ICA 25 Unruptured n/a None 1 2 treatments for residual 2
coiling
aneurysm

Repeat endovascular

35 40s L ICA 29 Unruptured n/a Stent-assisted coiling None 1 1 treatment for residual 3a

aneurysm

Multiple endovascular
Delayed stent-
36 70s L ICA 25.8 Ruptured III None 0 0 treatments for residual 2
assisted coiling
aneurysm

In-stent stenosis at 3

months, complete

37 40s R PCA 30 Unruptured n/a PED (x3) stent occlusion at 6 0 0 None 1

months, but

asymptomatic

BA + L PED (x3) + coil Secondary ischemic

38 80s 30 Unruptured n/a 3 4 None 2
VA occlusion of R VA stroke

Enterprise followed by
39 70s BA 40 Unruptured n/a None 0 0 None 2
2 PEDs + coils

At 3 months, PED
1 PED and 1
Cortical PCA foreshortened into 1 at 9
40 30s BA 30 Unruptured n/a enterprise distally, 3 3

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 vasospasm aneurysm, requiring months
coils to occlude L VA
additional PED

R hand weakness
41 60s L VA 30 Unruptured n/a PED (x9) 3 3 None 2
from L thalamic stroke

42 70s L ICA 30 Unruptured n/a PED (x4) None 0 0 None 1

43 70s L ICA 25 Unruptured n/a PED (x2) None 2 2 None 1

44 50s R PCOM 35 Unruptured n/a PED (x2) + coils None 0 0 None 2

45 70s R ICA 25 Unruptured n/a PED (x2) None 1 0 None 1

TABLE 1: Summary of cases

H&H, Hunt & Hess Scale; mRS, modified Rankin Scale; RS, Raymond Scale; L, left; SCA, superior cerebellar artery; ICA, internal
carotid artery; MCA, middle cerebral artery; PED, pipeline embolization device; R, right; VA, vertebral artery; IA, intra-arterial; TIA,
transient ischemic attack; SAH, subarachnoid hemorrhage; IPH, intraparenchymal hemorrhage; BA, basilar artery; ASA: acetylsalicylic
acid; IV, intravenous; n-BMA, n-butyl methacrylate; CN, cranial nerve; PCOM, posterior communicating artery.

Aneurysm characteristics
Mean aneurysm size was 29.9 mm (median/median: 28.1/28.3 mm; range: 25-50 mm). Eight
(18%) patients presented with aneurysmal subarachnoid hemorrhage (aSAH). In these cases,
the ruptured aneurysms had a mean/median diameter of 26.2/26 mm. In 37 (82%) patients, the
aneurysm was discovered as an incidental finding (mean/median diameter: 30.7/30 mm).

Of the aneurysms, 34 (76%) were found in the anterior cerebral circulation and 11 (24%) in the
posterior circulation (superior cerebellar artery, vertebral artery [VA], basilar artery, posterior
cerebral artery).

Aneurysm treatments
Of the 45 giant aneurysms in this series, 28 (62%) were treated with PED: 11 with a single PED
(24%) only, 1 with a single PED + coiling (2%), and 16 with more than one PED, with or without
coiling (36%). Eight (18%) aneurysms were treated with coiling alone, four (9%) with stent-
assisted coiling (including one delayed stent-assisted coiling), and two (4%) with balloon-
assisted coiling. The remaining three aneurysms were treated with other treatments including
parent vessel sacrifice (coiling and n-butyl methacrylate embolization) (2%), onyx embolization
(2%), and multiple stents (2%). Two cases successfully treated with multiple PEDs are shown in
Figures 1 and 2.

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 FIGURE 1: A young patient with an unruptured giant, fusiform,
dissecting left ICA aneurysm treated with multiple FDs.
(A-C): Three-dimensional reconstruction of digital subtraction angiography of the left ICA contrast
injection of the aneurysm (white arrows). (D) The aneurysm was treated by an implant of multiple
FDs as a construct from the left middle cerebral artery into the petrous segment of the left ICA
(white arrow). (E, F) AP view of the left ICA injection before treatment (E) and one year after
treatment with FD (F) demonstrating complete occlusion of the aneurysm and reconstruction of the
ICA (white arrows).

ICA, internal carotid artery; FD, flow diverter; AP, anterior-posterior

FIGURE 2: A patient with an unruptured giant cavernous and

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 supraclinoid aneurysm of the right ICA. The aneurysm was
treated by implant of a construct of FD devices.
(A) Three-dimensional reconstruction of digital subtraction angiography of the right ICA contrast
injection of the aneurysm (white arrow). (B) XperCT reconstruction of the right ICA contrast injection
after implant of a construct of multiple FD devices from the ICA terminus to the petrous segment of
the right ICA (white arrows). (C) Digital subtraction angiography in AP and lateral views before the
implant (white arrows). (D) Follow-up angiography in AP and lateral views one year after treatment
demonstrating complete occlusion of the lesion with reconstruction of the artery (white arrows).

ICA, internal carotid artery; FD, flow diverter; AP, anterior-posterior

The distribution of treatments for ruptured aneurysms compared with unruptured aneurysms
was quite different. All eight ruptured aneurysms were treated with coiling, and none with PED
or other treatments. Five (63%) were treated with coiling alone, 2 (25%) with stent-assisted
coiling, and 1(13%) with balloon-assisted coiling. In contrast, only 3 (8%) of 37 unruptured
aneurysms were treated with coiling alone, 2 (5%) with stent-assisted coiling, and 1 (3%) with
balloon-assisted coiling. Twenty-eight (76%) unruptured aneurysms were treated with PEDs: 21
(57%) with PED only and 7 (19%) with PED + coiling. The remaining three were treated with the
other treatments as described in the previous paragraph. In summary, ruptured aneurysms
were treated only with coiling or assisted coiling, and unruptured aneurysms were treated
primarily with PEDs.

Complications
Mortality
Overall, mortality for this series was 3/45 (7%): one occurred in a patient with aSAH secondary
to the giant aneurysm (Hunt and Hess grade IV) and two occurred in unruptured aneurysms. No
mortality was procedure-related. In particular, one patient (case 14) was affected by chronic
alcoholism and cocaine addiction, who presented with aSAH (Hunt and Hess grade IV)
secondary to a ruptured 26-mm right middle cerebral artery (MCA) aneurysm. This aneurysm
was treated by coil embolization; however, the patient never recovered to a good neurological
status and subsequently developed multiple subarachnoid hemorrhage (SAH) and ICU-related
complications and was made comfort care by the family. Another patient (case 6) presented
with a 35-mm unruptured right VA aneurysm treated with coil embolization subsequently
expired secondary to medical complications related to advanced Parkinson’s disease. The third
patient (case 21), with a 35.8-mm unruptured left ICA aneurysm treated with three PEDs, died
several months later from causes unrelated to the procedure.

Stroke
Five (11.1%) patients experienced ischemic strokes, two had ruptured aneurysms, and three
had unruptured aneurysms. The first one presented with aSAH secondary to a 25.3-mm
ruptured MCA aneurysm, was treated with coiling, and needed rescue treatment consisting of a
flow diverter for aneurysmal re-growth (case 3). This patient recovered completely from the
neurological deficit and had a 90-day mRS score of 0. The second patient presented with aSAH
(Hunt and Hess grade IV) secondary to a ruptured 26.4-mm right ICA aneurysm, was treated
with coiling, and needed rescue treatment with intravenous Integrilin (case 33). This patient
had a 90-day mRS score of 3. Another patient (case 24) presented with a 25.3-mm unruptured
right MCA aneurysm was treated with two PEDs and coiling and then had complete PED
occlusion and right lentiform and caudate nucleus infarct with clinical worsening (pre-
procedure mRS score = 2; 90-day mRS score = 4). The fourth patient had a 30-mm unruptured
basilar and left VA aneurysm treated with three PEDs and coiling of the right VA (case 38). The

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 pre-procedure mRS score was 3, which worsened to 4 at 90 days. The fifth patient presented
with a 30-mm unruptured left VA aneurysm that was treated with nine PEDs (case 41). A left
thalamic stroke occurred causing right hand weakness, but the mRS score at 90 days was 3,
which was the same as pre-procedure. A patient who had a 36-mm unruptured basilar tip
aneurysm treated with multiple stents had thrombosis of small perforators with subsequent
reperfusion hemorrhage (case 29). The patient received anticoagulation and IV Integrilin as
rescue therapy. This patient was lost to follow-up before the 90-day mRS score could be
obtained.

Follow-up
Clinical Follow-up
At the time of treatment, 14 (31.1%) of 45 patients had no disability (mRS score = 0), 21 (46.7%)
had minimal disability (mRS score = 1-2), 4 (8.9%) had moderate disability (mRS score = 3), 2
(4.4%) had moderately severe disability (mRS score = 4), and 4 (8.9%) had severe disability (mRS
score = 5).

Thirty-five (82.2%) patients were available for clinical follow-up at 90 days; three had died and
seven were lost to follow-up. Thirty (85.7%) patients had good outcomes (90-day mRS score ≤
2). Three (8.6%) patients had a moderate disability (90-day mRS score = 3). Two (5.7%) of the
remaining patients had moderately severe disability (90-day mRS score = 4). Of the 35 patients
with 90-day follow-up, there were 2 patients who had some disability that improved from
baseline (mRS score of case 10 = 5 to 2; mRS score of case 33 = 5 to 3).

Angiographic Follow-up
Overall, 33/45 (73.3%) patients were available for six-month angiographic follow-up. In
addition, 23 (70%) patients had a RS score of 1, 7 (20.9%) had a score of 2, and 3 (9.1%) had a
score of 3.

Comparison of Outcomes in Anterior versus Posterior

Circulation Aneurysms
Ischemic stroke occurred in 3/34 anterior circulation cases (9%) and 2/11 posterior circulation
case (18%). Mortality occurred in 2/34 in anterior circulation (6%) and 1/11 posterior cases
(9%). Ninety-day mRS score was available for 29 of 34 anterior cases (85%) and 9 of 11 cases
posterior cases (82%), which is a comparable rate of follow-up between groups using the chi-
square test (p > 0.05). The proportion of good clinical outcome (mRS score ≤ 2) was 25/29 (86%)
for anterior circulation cases and 5/9 (55%) for posterior circulation cases, a difference that was
statistically significant (χ2 [1, N = 38] = 3.88; p < 0.05). At six months, the RS was available for
24/34 anterior circulation cases (71%) and 8/11 (73%) posterior circulation cases, which, again,
is a comparable rate of follow-up (p > 0.05). The proportion of good angiographic outcome (RS
= 1) for anterior circulation aneurysms was 19/24 (79%) compared with 3/8 (38%) for posterior
circulation aneurysms. This difference was also statistically significant (χ2 [1, N = 32] = 4.85; p
< 0.05). These results are summarized in Table 2.

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 90-day modified Rankin Scale Raymond Scale

Aneurysm type Treatment Good (0-2) Poor (3-6) n/a Good (1) Poor (2-3) n/a

PED only 15 2 1 14 1 3

PED + coil 2 0 1 1 0 2
Anterior
Coil only 8 2 2 5 4 3

Other 0 0 1 0 0 1

PED only 2 1 0 1 2 0

PED + coil 1 2 1 1 2 1
Posterior
Coil only 1 1 0 0 1 1

Other 1 0 1 1 0 1

TABLE 2: Comparison of treatment outcomes in anterior versus posterior circulation

PED, pipeline embolization device

Comparison of Treatments in Unruptured Aneurysms Only

At 90 days, in patients with unruptured aneurysms who received PED only, 16/19 (84%) had
good clinical outcome (mRS score ≤ 2). In comparison, 5/6 (83%) of patients with unruptured
aneurysms who received coiling alone had a good clinical outcome and 4/6 (67%) patients who
had a PED + coiling had a good clinical outcome. At six months, 15/17 (88%) patients who
received PED only had an RS score of 1, 2/5 (40%) patients who received PED + coiling had an
RS score of 1, and only 2/5 (40%) of those who received coiling alone had an RS score of 1
(Table 3). Using the chi-square analysis, there was no difference in the proportion of patients
with good (mRS score = 0-2) versus poor (mRS score = 3-6) clinical outcomes across treatment
groups (p = 0.81). However, the proportion of good (RS score = 1) vs. poor (RS score = 2-3)
radiographic outcomes was statistically significantly better for the group treated with PED
alone compared with those treated with PED + coiling or coiling alone (χ2 [1, N = 31] = 7.02; p <
0.05).

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 90-day modified Rankin Scale Raymond Scale

Aneurysm type Treatment Good (0-2) Poor (3-6) n/a Good (1) Poor (2-3) n/a

PED only

PED + coil
Ruptured
Coil only 4 2 2 3 2 3

Other

PED only 16 3 1 15 2 3

PED + coil 4 2 2 2 3 3
Unruptured
Coil only 5 1 0 2 3 1

Other 1 0 2 1 0 2

TABLE 3: Comparison of treatment outcomes in ruptured versus unruptured

aneurysms
PED, pipeline embolization device

Discussion
Our cohort of 45 ruptured and unruptured GIAs treated by the endovascular approach
represents a contemporary treatment outcome of these lesions in three medical centers. The
overall mortality rate was 6.7% (3/45), with none of them being procedure-related. Five (11.1%)
patients experienced ischemic strokes and only two had a 90-day mRS score of ≥3. Of the 35
patients available at 90-day follow-up, 85.7% (30/35) had good clinical outcomes (90 days mRS
score ≤ 2), and 2 patients were improved from baseline. Complete aneurysm occlusion was
demonstrated in 70% (23/33) of patients at six months follow-up through DSA.

In the literature, ruptured and unruptured GIAs are associated with severe neurological
morbidity and mortality. In particular, the RR for untreated, unruptured GIAs was reported to
be 8-10% per year, with a mortality of 65-100% at two to five years follow-up [10,11]. When
GIAs are treated by microsurgical clipping, the mortality rates of both ruptured and unruptured
GIAs were reported at 6- 22% [6,10]. As such, our mortality rate for endovascular treatment of
GIAs was better than the rate described for surgical clipping. Several authors reported good
clinical outcomes when GIAs were treated by an endovascular approach. In particular, Cekirge
et al. reported a complete occlusion rate of 76% post-procedure, 80% at three to six months,
and 93% at two to five years in the giant aneurysm group by using liquid embolic agents [14].
However, the authors did not state the rates of good clinical outcomes specifically for the giant
aneurysm group. Sluzewski et al. reported good clinical outcomes in 79% of very large and giant
aneurysms at a median follow-up at 50 months, though 41% of aneurysms were still
incompletely occluded even after repeated coiling [15].

The work on flow diversion technology by Wakhloo and Gounis and by Lieber et al. undoubtedly
was a major step forward for the treatment of intracranial aneurysms [16,17]. The safety and
efficacy of PED have been demonstrated in numerous studies. Pooled analysis of such studies

2020 Linfante et al. Cureus 12(5): e8290. DOI 10.7759/cureus.8290 11 of 15

 has shown that PED is associated with a low risk of complications and high angiographic
occlusion rates. Nelson et al. showed 93% occlusion rates at six-month angiographic follow-up,
with only 6.5% of patients experiencing major neurological complications when treated with
PED [18]. In the PUFS study, the mean aneurysm size was 18.2 mm, with 22 (20.4%) of 108
aneurysms being giant. Complete occlusion in the entire cohort was 73.6% and 86.6% at 180-
day and one-year follow-up, respectively [2]. Similarly, in our study, complete occlusion was
demonstrated in 88% of patients at six months. In the IntrePED study, 66 aneurysms (7.3%)
were giant [13]. At 30 days, the morbidity and mortality rates were higher in patients with giant
aneurysms (25.8%) compared with large (8.8%) and small (5.4%) aneurysms. The giant
aneurysm group demonstrated higher rates of spontaneous ruptures and ischemic strokes when
compared with other groups [13]. Similarly, in a meta-analysis of spontaneous aneurysm
rupture after flow diversion treatment, the relative RR was 23% for GIAs [19]. Lastly, in a
retrospective review that included large and GIAs treated with PED or PED + coils, the authors
found complete or near-complete occlusion at the last follow-up in 77% of cases. Of the
patients, 12% had symptomatic ischemic complications and 8% had symptomatic hemorrhagic
complications, and the overall mortality was 6% [20]. However, there were no separate results
for GIAs, nor were comparisons made between large and giant aneurysms. In our study, the rate
of ischemic stroke was 5% (1/21) and the mortality rate was 5% (1/21). Our results strengthen
the current body of PED literature, which indicates that PED is safe and effective for the
treatment of unruptured GIAs.

Coiling alone is a treatment option for GIAs, but it has poor long-term outcomes because giant
aneurysms are often incompletely occluded and require repeated coiling [4]. For our ruptured
GIAs treated with coiling, we found that 67% had favorable clinical outcomes at 90 days and
60% had complete occlusion at six months. In unruptured GIAs, 83% had favorable clinical
outcomes at 90 days, although only 40% exhibited complete occlusion at six months when
treated with coiling alone. In comparison, 89% of cases that received any PED treatment (with
or without coiling) had a good clinical outcome at 90 days and 92% had complete occlusion at
six months. In addition, three of five ischemic strokes were in patients who were treated with
coiling only (two ruptured, one unruptured). In the report by Park et al., PED in combination
with coiling was shown to result in higher neurological morbidity and required longer
procedural time versus PED alone [21]. In our study, there were eight cases of PED with coiling;
four of six cases that followed up at 90 days had good clinical outcome, and out of the five
follow-ups at six months, only two showed complete occlusion. Stent-assisted coiling and PED
has shown to be equally effective, with no significant differences in complications and
angiographic outcomes [22]. Interestingly, we found that all three of the cases treated with
stent-assisted coiling had incomplete occlusion at six months, even though they all had a good
clinical outcome at 90 days. There was one case with a 90-day mRS score of 3 that did not
follow-up at six months.

In this series, coiling with or without PED was guided by operator preference. Usually, if
possible, coils were placed in the aneurysmal sac. In case of a ruptured GIA, coiling is usually
the first approach in order to avoid dual anti-platelet regimen in a patient with an acute SAH.

Overall, our results of PED in unruptured GIAs are similar to those previously reported in the
setting of controlled trials [23]. Our current analysis suggests a role of the combination of PED
and coils in achieving high occlusion rates. Given the poor natural history of GIAs, a careful
study of each patient’s GIA anatomy and relationships with afferent and efferent vessels is
recommended to determine the optimum treatment.

Limitations
The present cohort has all the inherent limitations of a retrospective analysis of patients
treated endovascularly over an eight-year period. The choice of treatment and follow-up timing

2020 Linfante et al. Cureus 12(5): e8290. DOI 10.7759/cureus.8290 12 of 15

 were based on the operating physician preference. The perioperative management and choice
of rescue treatment were also based on physician preference. Because of these treatment
choices, all of the ruptured aneurysms were treated with coiling and none were treated with
PED. Therefore, direct comparisons between treatment types in ruptured and unruptured
aneurysms could not be made. In addition, no GIAs were treated at these centers with surgical
clipping; therefore, comparisons with conventional surgery could not be made. However,
angiographic follow-up was consistent in all centers, and patients had conventional DSA at the
time of admission and at the six-month follow-up period. Several patients were lost to follow-
up by six months. The study does not take into account advances in technology that have
occurred in the last eight years. All of the operators from the centers selected for this analysis
are high-volume centers for endovascular treatment for complex aneurysms; therefore, these
results may not be generalizable to other lower volume centers.

Conclusions
Our study suggests that endovascular treatment of GIAs either by coil embolization or PED
(±coiling) is feasible and can be accomplished with relatively low complication rates and
moderate long-term clinical and radiographic outcomes. Future studies with current
endovascular technology may be needed to define the best approach for these lesions.

Additional Information
Disclosures
Human subjects: Consent was obtained by all participants in this study. Baptist Health South
Florida issued approval 10-060. The current analysis was approved by Institutional Review
Boards of the University at Buffalo, Baptist Health South Florida, and Baylor College of
Medicine with a waiver of informed consent. Animal subjects: All authors have confirmed that
this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with
the ICMJE uniform disclosure form, all authors declare the following: Payment/services info:
All authors have declared that no financial support was received from any organization for the
submitted work. Financial relationships: Adnan Siddiqui declare(s) personal fees from Amnis
Therapeutics. Italo Linfante declare(s) stock/stock options from InNeuroCo. Adnan Siddiqui
declare(s) personal fees from Apama Medical. Adnan Siddiqui declare(s) personal fees from
BlinkTBI, Inc. Adnan Siddiqui declare(s) personal fees from Buffalo Technology Partners, Inc.
Adnan Siddiqui declare(s) personal fees from Cardinal Consultants, LLC. Adnan Siddiqui
declare(s) personal fees from Cerebrotech Medical Systems, Inc. Adnan Siddiqui declare(s)
personal fees from Cognition Medical. Adnan Siddiqui declare(s) personal fees from
Endostream Medical, Ltd. Adnan Siddiqui declare(s) personal fees from Imperative Care. Adnan
Siddiqui declare(s) personal fees from International Medical Distribution Partners. Adnan
Siddiqui declare(s) personal fees from Q'Apel Medical, Inc,. Adnan Siddiqui declare(s) personal
fees from Neurovascular Diagnostics, Inc. Adnan Siddiqui declare(s) personal fees from
Rebound Therapeutics Corp. Adnan Siddiqui declare(s) personal fees from Rist Neurovascular,
Inc. Adnan Siddiqui declare(s) personal fees from Serenity Medical, Inc. Adnan Siddiqui
declare(s) personal fees from Silk Road Medical. Adnan Siddiqui declare(s) personal fees from
StimMed. Adnan Siddiqui declare(s) personal fees from Synchron. Adnan Siddiqui declare(s)
personal fees from Three Rivers Medical, Inc. Italo Linfante declare(s) stock/stock options from
Three Rivers Medical, Inc. Adnan Siddiqui declare(s) personal fees from Viseon Spine, Inc.
Adnan Siddiqui declare(s) personal fees from Boston Scientific. Adnan Siddiqui declare(s)
personal fees from Canon Medical Systems USA, Inc. Adnan Siddiqui, Guilherme Dabus
declare(s) personal fees from Cerenovus. Adnan Siddiqui declare(s) personal fees from
Corindus, Inc. Adnan Siddiqui declare(s) personal fees from Integra Life Sciences Corp. Italo
Linfante, Guilherme Dabus, Adnan Siddiqui declare(s) personal fees from Medtronic. Adnan
Siddiqui, Guilherme Dabus declare(s) personal fees from MicroVention. Adnan Siddiqui
declare(s) personal fees from Northwest University. DSMB Chair for the HEAT Trial. Adnan

2020 Linfante et al. Cureus 12(5): e8290. DOI 10.7759/cureus.8290 13 of 15

 Siddiqui, Guilherme Dabus declare(s) personal fees from Penumbra. Adnan Siddiqui declare(s)
personal fees from Rapid Medical. Adnan Siddiqui declare(s) personal fees from VasSol. Adnan
Siddiqui declare(s) personal fees from W.L. Gore & Associates. Adnan Siddiqui declare(s)
personal fees from Medical University of South Carolina. National PI/Steering Committee for
the POSITIVE trial. Guilherme Dabus declare(s) stock/stock options from Surpass. Italo
Linfante, Adnan Siddiqui, Michael McDermott declare(s) personal fees from Stryker. Other
relationships: All authors have declared that there are no other relationships or activities that
could appear to have influenced the submitted work.

Acknowledgements
The authors would like to acknowledge Maygret Ramirez, MSN, APRN, FNP, SCRN, Virginia
Ramos, MSN, APRN, FNP-BC, CNRN, SCRN, and Felix Chin for collecting and entering data for
the registry. We also want to acknowledge Dr. Ricardo Hanel who was the Proctor for one of the
cases.

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