Keywords
intracranial aneurysm - clipping - aneurysm recurrence - subarachnoid hemorrhage
Introduction
The annual risk of recurrence is very low, ranging from 0.02 to 0.52%[1]
[2]
[3] for a completely clipped intracranial aneurysm (IA), but substantially higher, ranging
from 0.38 to 7.3% in a known residual.[1]
[2]
[3]
[4] There is growing consensus based on these figures that long-term surveillance in
patients with residual IAs after clip ligation is needed. However, no protocol is
yet established that defines timing or optimal modality of follow-up imaging. Time
to IA recurrence after clipping averages nearly a decade[5]
[6]
[7] and rate of regrowth is likely slow,[8] less than 0.5 mm per year in regrowing residuals in a recent cohort.[2] Significant causes for increased unexpected findings (including IA remnants) in
postsurgical digital subtraction angiography (DSA) can include location, complex morphology,
and large aneurysm size.[9]
[10]
[11]
Robust risk factors for IA recurrence and growth of IA remnants after clip ligation
are not established. Our case report describes an early asymptomatic recurrence of
less than 1 year in a 20-year-old woman who underwent clip ligation of a ruptured
anterior communicating artery (AComA) aneurysm. We then review the literature to summarize
findings in similar cases of early recurrence and hypothesize potential predictors
that warrant early imaging follow-up.
Case Report and Review of the Literature
Search Strategy
The literature search has been performed in accordance with PRISMA guidelines guidelines.[12] Per June 15th, 2016, the PubMed database was searched to identify all case reports
and case series of patient with local IA recurrence after microsurgical neck clipping.
This search strategy was used as a subproject of a large systematic meta-analysis
on de novo IA formation and recurrence after neck clipping.[13]
Clinical Presentation
A 20-year-old woman patient presented with syncope and impaired consciousness with
a Glasgow Coma Scale 12, severe headache, meningismus, recurrent vomiting, and hypertensive
crisis but had no focal neurological deficits. Medical history revealed no report of sentinel headache, no evidence of epileptic
seizure, and no IA risk factors (i.e., negative family history, nonsmoker, no hypertension,
absent drug abuse). The patient was otherwise healthy and was not taking any medications.
There were no signs for polycystic kidney disease or Marfan syndrome. Magnetic resonance imaging findings demonstrated extensive subarachnoid hemorrhage
(SAH) (Fisher grade 4) with an acute left-sided 2-mm subdural hematoma. Magnetic resonance
angiography revealed a small irregularly shaped IA of the AComA complex as putative
source of SAH. With this diagnosis, the patient was referred to our institution.
Admission Workup
At admission, the patient was immediately taken to the hybrid operating room (hOR).
Four-vessel cerebral DSA including standard views, additional IA specific views, and
a volumetric sequence to reconstruct three-dimensional (3D) angiographic and multiplanar
computed tomography (CT) images confirmed a small (3 × 3.5 mm) relatively broad-based
AComA aneurysm predominantly supplied from the left anterior cerebral artery. 3D-DSA did not detect any additional IA. The aneurysm itself had an irregularly shaped surface that included multiple blebs
and a small secondary aneurysm protruding from the fundus (daughter aneurysm). The
admission workup is summarized in [Fig. 1].
Fig. 1 Admission workup for 20-year-old patient. Initial magnetic resonance angiogram revealed
a small ruptured left-sided anterior communicating artery aneurysm (A). Subsequent four-vessel two-dimensional digital subtraction angiography (2D-DSA)
confirmed the single aneurysm predominantly supplied from the right anterior cerebral
artery (B). 3D-DSA clarified the angioarchitecture and visualized a small (3 × 3.5 mm) relatively
broad-based aneurysm (C, left inset). Virtual rotation revealed an irregular shaped surface with posteriorly
projecting multiple blebs and tiny daughter aneurysms protruding from the aneurysm
fundus (C, right inset, *).
Treatment
With consensus between the attending interventional neuroradiologist and neurosurgeon,
the patient underwent a left pterional craniotomy and IA clipping in the hOR. During
visual inspection after pilot clip ligation, the aneurysm ruptured close to the base.
The initial clip was repositioned and a second clip was placed. Repeat visual inspection,
Doppler sonography, and indocyanine green video angiography demonstrated complete
IA occlusion and patent A2 segments. Intraoperative 3D-DSA confirmed complete obliteration
of the irregularly shaped regions of the aneurysm and revealed a small (1 × 1.5 × 1
mm) posteriorly projecting IA remnant that was surgically unsuitable for clip replacement
or wrapping ([Fig. 2]). Postoperatively, the patient initially demonstrated clinical improvement with
increased consciousness and normal findings on day 1 postoperative CT scan. During
the next 3 days, she became hydrocephalic and underwent external ventricular drainage,
and developed medically refractory delayed cerebral vasospasm. On days 6, 8, and 12
after IA rupture, endovascular treatment was used as a rescue therapy with intra-arterial
nimodipine infusion. During this period, the patient developed prolonged nonconvulsive status epilepticus, progressive brain swelling, and intractable intracranial pressure that necessitated
decompressive hemicraniectomy. The patient̀s condition stabilized, and she was discharged
on day 44 to a rehabilitation facility (modified Rankin Scale 4).
Fig. 2 Intraoperative remnant. Standard intraoperative two-dimensional digital subtraction
angiography (2D-DSA) in anteroposterior (A) and lateral (B) projections shows the small remnant is barely visible and obscured by surrounding
vessels. In multiplanar intraoperative 3D-DSA (C), viewing angles are unrestricted. Clipped intracranial aneurysm complex can be virtually
rotated in any direction (C, inset) to identify and measure the small dog-ear remnant (1 × 1.5 × 1 mm) without
interference of clip masses or adjacent vessels.
Follow-Up
Two months after rehabilitation and complication-free period after reimplantation
of the autologous bone flap, the patient showed good recovery (modified Rankin Scale
2) but declined the planned 6-month follow-up imaging. At annual follow-up examination,
angiography demonstrated a large (7 × 11 mm) recurrence. With consensus of our interdisciplinary
team, the patient underwent coiling of the regrown IA. At 6- and 18-month follow-up,
DSA studies demonstrated complete IA occlusion ([Fig. 3]).
Fig. 3 Recurrence, retreatment, and follow-up. Follow-up of two-dimensional digital subtraction
angiography (2D-DSA) and 3D-DSA 12 months after clipping depicting a large recurrence
(7 × 10 mm) with small neck (3 mm) exactly at the site of the intraoperatively documented
aneurysm remnant (A and B). After coiling, this aneurysm showed stable, complete occlusion at 6 and 18 months
(C) after retreatment.
Discussion
Despite the general late recurrence and slow growth rate of IA remnants after microsurgical
clip ligation, our case report demonstrates a rare instance of an early and rapid
IA recurrence from a tiny 1-mm aneurysm remnant. Although risk factors for remnants
after clipping are known, how these factors cause recurrence and growth of such IA
remnants is not established.
Location as Risk Factor for IA Remnant
Intracranial location has been recognized as a predictor of incomplete aneurysm occlusion
after clipping.[9]
[10]
[11]
[14]
[15] Compared with the middle cerebral artery (MCA), higher rates of incomplete occlusion
after clip obliteration were associated with aneurysms located at the AComA complex
or posterior circulation. Recently, a multivariate analysis confirmed IA location
(ACA > ICA > PC > MCA) as a significant risk factor for leaving an IA remnant post-clipping.
Along with our patient's aneurysm located at the AComA, our literature review identified
early postoperative recurrences located at the AComA complex in four cases, basilar
artery in two cases, and posterior communicating artery in one case. A growing body
of evidence suggests that aneurysms of the AComA harbor an increased risk of rupture.[16]
[17] One hypothesis is that underlying biological factors not only influence risk of
rupture of an AComA aneurysm but also increase risk of recurrence and growth after
clipping.[18]
Age as Risk Factor for Remnant Growth
In a 2016 multivariate analysis, Jabbarli et al determined that age was an independent
risk factor for remnant growth.[19] In review of variables of patient characteristics, the authors identified that those
less than 45 years of age were at risk of higher rates of remnant growth (odds ratio > 33).
In a large population-based cohort, Lindgren et al found younger age at first IA diagnosis
was significantly associated with de novo IA formation.[20] In our literature review, five of seven cases with early IA recurrence were younger
than 50 years of age ([Table 1]) and our patient was exceptionally young at 20 years of age.
Table 1
Patient characteristics of IA recurrences within 1 year after clip ligation
|
Author/year
|
Interval (months)
|
Age (years)
|
Sex
|
Rupture status
|
Location
|
IA occlusion grade/imaging modality
|
|
Adamson and Batjer(1988)[21]
|
2
|
50
|
m
|
SAH
|
BA
|
Complete occlusion/intraoperative 2D-DSA
|
|
Asgari et al (2003)[22]
|
1
|
66
|
F
|
SAH
|
AComA
|
Complete occlusion/postoperative 2D-DSA
|
|
Cekirge et al (2000)[23]2000
|
2
|
40
|
m
|
SAH
|
AComA /
|
Not reported
|
|
el-Beltagy et al (2010)[5]
|
12
|
40
|
F
|
SAH
|
PCA
|
Complete occlusion/postoperative 2D-DSA
|
|
12
|
49
|
F
|
SAH
|
BA
|
Complete occlusion/postoperative 2D-DSA
|
|
Spiotta et al (2013)[6]
|
1
|
48
|
F
|
SAH
|
AComA
|
Not reported
|
|
4
|
62
|
m
|
SAH
|
AComA
|
Not reported
|
|
Present case report
|
12
|
20
|
F
|
SAH
|
AComA
|
Dog-ear remnant/3D-iDSA, ICGA
|
Abbreviations: 2D-DSA, two-dimensional digital subtraction angiography; 3D-iDSA, Three-dimensional
intraoperative digital subtraction angiography; AComA, anterior communicating artery;
BA, basilar artery; IA, intracranial aneurysm; ICGA, indocyanine green angiography;
PComA, posterior communicating artery; SAH, subarachnoid hemorrhage.
Size as Risk Factor for Remnant Regrowth
Although some authors found increased risk of IA recurrence with increasing size of
residual aneurysm,[19]
[24]
[25] others found no association between remnant size and risk of regrowth.[2]
[4] Our patient's residual aneurysm was very small (1 × 1 mm). In the seven cases of
early recurrence in our review, three cases did not specify whether a remnant was
present, and four cases deemed complete occlusion of the IA. However, small remnants
could have been missed. Compared with the much higher detection rate of small-sized
IA remnants[26]
[27] with 3D-DSA, 2D intra- or postoperative DSA or CT angiography is more limited in
ruling out such small remnants. Like our patient, higher detection rates of small residuals are now more likely because
of intra- or postoperative 3D-DSA.[28]
Other Potential Risk Factors for IA Remnant Growth
In the most recent series from a prospective database with long-term follow-up by
means of DSA, no association was found between postoperative residual growth and multiple
IAs, fusiform morphology, clip reconstruction, or SAH.[2] In a 2013 series of 26 patients with IA recurrences, Spiotta et al noted 21 patients
with a positive rupture status.[6] They hypothesized that the biological difference between ruptured and unruptured
IAs was the determining factor for IA recurrence after clipping. All reporting early
(< 1 year) IA recurrences (including our case) to date were found in patients with
a previous history of SAH from the clipped IA.
Discussion regarding risk factors for IA remnant growth is complicated by what defines
postoperative IA residual and recurrence. For example, Burkhardt et al grouped postoperative
residuals into intentional and unintentional remnants.[2] Their data suggest a benign nature of intentional residuals that are left to preserve
branch arteries. From a biological point of view, residuals left intentionally to
preserve perforators or branching arteries presumably consist of healthy vessel walls,
whereas unintended remnants represent diseased IA walls that are more likely to undergo
further degeneration and eventually growth. In our patient, the unintended remnant
represented a tiny bleb of the IA wall and was not part of a parent artery or small
perforator. An earlier hypothesis proposed that pathobiological differences of IA
remnants contribute to the delay (time course) between surgery and recurrence: that
is, an early, more rapid recurrence resulted from a persistent wall weakness (unintentionally
left IA residual) and late, slower recurrence from de novo vessel wall degeneration.[6]
In summary, some evidence exists that young age and positive rupture status predisposes
a patient for IA remnant growth. It remains controversial and partially unknown whether
IA (size, morphology, clip reconstruction technique, flow dynamics) and patient-specific
factors (multiple IA, previous SAH, family history, smoking, hypertension) known to
influence growth of unruptured IA likewise influence growth of IA remnants. Although
most IA remnants after clipping grow slowly, early recurrence may represent a more
aggressive biological behavior that warrants special attention in younger patients,
positive rupture status, and unintended remnant of any size. In such a constellation,
early imaging follow-up within the first 6 months may be warranted to rule out early
IA recurrence.
