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Late recurrence of subarachnoid hemorrhage and intracranial aneurysms

Official reprint from UpToDate

www.uptodate.com 2014 UpToDate
Late recurrence of subarachnoid hemorrhage and intracranial aneurysms
Authors
Robert J Singer, MD
Christopher S Ogilvy, MD
Guy Rordorf, MD

Section Editor
Deputy Editor
Jose Biller, MD, FACP, FAAN, FAHA Janet L Wilterdink, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2014. | This topic last updated: Jul 31, 2013.
INTRODUCTION Aneurysmal subarachnoid hemorrhage (SAH) is often a devastating event. However,
therapeutic advances have added to the armamentarium for treating this malignant process. As case-fatality rates
decline, attention is increasingly turned to the management of long-term complications. One of these is the
enduring risk of recurrent SAH, which can occur despite successful endovascular or surgical treatment of the
ruptured aneurysm.
This topic discusses the risk of recurrent aneurysm formation and subarachnoid hemorrhage after a patient has
been treated for an initial subarachnoid hemorrhage. Other topics address acute aspects of aneurysmal
subarachnoid hemorrhage, as well as the management of patients with unruptured intracranial aneurysms, and
aneurysm screening in other high risk populations. (See "Clinical manifestations and diagnosis of aneurysmal
subarachnoid hemorrhage" and "Treatment of aneurysmal subarachnoid hemorrhage" and "Unruptured intracranial
aneurysms" and "Screening for intracranial aneurysm".)
EPIDEMIOLOGY Cumulative 8 to 10 year incidences of late rebleeding (more than one year after initial SAH)
vary from 0.1 to 3.2 percent [1-5]. The risk of SAH recurrence has been estimated to be 15 to 22 times higher than
the expected rate of a first SAH in a healthy age, sex matched cohort [2,4].
Independent risk factors for recurrent SAH in one study were current smoking, younger age, and multiple
aneurysms at the time of the initial SAH [2]. Hypertension was an additional important risk factor for aneurysm
regrowth or de novo aneurysm formation in another retrospective study [6]. Cigarette smoking and hypertension are
also established risk factors for both unruptured intracranial aneurysms and aneurysmal subarachnoid hemorrhage.
(See "Clinical manifestations and diagnosis of aneurysmal subarachnoid hemorrhage" and "Unruptured intracranial
aneurysms".)
CAUSES Recurrent SAH may result from recurrence of the treated aneurysm, rupture of another pre-existing
aneurysm in a patient with multiple aneurysms, and de novo aneurysm formation.
In the International Subarachnoid Aneurysm Trial (ISAT), 24 rebleeds occurred in 2004 patients followed for a mean
of 9 years after treatment; 13 were from the treated aneurysm, 4 from a pre-existing, untreated aneurysm, and 6
were from new aneurysms (the pre-existing status of one aneurysm was unknown) [1].
Recurrence of the treated aneurysm Endovascularly-treated patients appear to be at somewhat higher risk of
rebleeding from the original aneurysm than surgically-treated patients [1,3,7]. In the ISAT, 10 of the 13 recurrent
SAH from the original aneurysm were in the endovascular treatment group [1]. This is consistent with follow-up
imaging studies that suggest that aneurysm recurrence appears to be more common in patients who undergo
endovascular treatment as opposed to surgical clipping:
In one case series, the index aneurysm was retreated during the first year in 8 percent of 299 patients
treated with coiling and 2 percent of 711 patients treated surgically [3]. No surgically-clipped aneurysm was
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retreated after the first year, whereas 4.5 percent of endovascularly-treated patients required recoiling in the
second year and 1 percent were recoiled each year in subsequent years.
Among the 2108 patients originally treated in ISAT, late retreatment was more frequent after endovascular
coiling than after clipping (8.6 versus 0.9 percent) [8]. The mean time to late retreatment after endovascular
coiling was 21 months.
In a retrospective analysis of 501 aneurysms treated with endovascular coiling in 466 patients, 34 percent of
aneurysms had recurrences at a mean of 12 months after treatment [9].
A systematic review of published case series reported on aneurysm reopening after coiling in 8161
aneurysms: 91 percent were occluded after the first treatment; reopening occurred in 21 percent and
retreatment was performed in 10 percent [10].
A single centers experience with coiling 818 patients with aneurysm, 404 of whom had presented with SAH,
revealed recanalization rate of 20.9 percent on follow-up angiography performed between 6 to 18 months after
the initial treatment [11].
In a systematic review of 71 studies of endovascular treatment of 1316 unruptured aneurysms followed for up
to three years, recurrence was noted in 24 percent [12].
The above studies suggest that aneurysm recurrence occurs in 9 to 34 percent of endovascularly-treated
aneurysms. Risk factors for aneurysm recurrence reported in more than one study included larger lumen size (>10
mm), larger aneurysm neck size, and incomplete occlusion [7-11,13-15]. The mechanism of aneurysm recurrence
in this setting may be related to compaction of coils over time and/or to aneurysm sac growth [16]. One
randomized trial found that the use of hydrogel-coated coils (designed to improve packing and stability) was
associated with fewer cases of aneurysm recurrence compared to standard bare platinum coils (24 versus 33
percent) [17]. The highest risk for recurrence of a coiled aneurysm appears to be in the first six months and is low
after two years [3,15,18,19]. Most of these aneurysm recurrences are not associated with rupture and SAH; the
estimated annual hemorrhage rate after coiling of a ruptured aneurysm is between 0.1 and 3 percent [3,9,11-13,18].
Recurrence of an aneurysm that was successfully surgically clipped appears to be relatively rare [1-3,20]. In a
study of 112 patients (140 clipped aneurysms) who had agreed to undergo cerebral angiography at a mean of nine
years after clipping, 4 aneurysm regrowths (3 percent) were detected [21]. In another study of 610 patients, treated
with surgical clipping, follow-up computed tomographic angiography (CTA) 2 to 18 years after the index SAH
revealed an aneurysm at the clip site in 24 patients (4 percent) [22]. Recurrent SAH attributed to a previously
clipped aneurysm is even less common [1-3,18,20,22]. As an example, in a cohort of 752 patients with aneurysmal
SAH and successful clipping after a mean follow-up of 8 years, only 4 of the 18 subsequent recurrent SAH (0.5
percent) were associated with a recurrent aneurysm at the clip site [2]. In another series of 711 patients, none of
the surgically clipped aneurysms was associated with rerupture over a mean of 4.4 years followup [3].
De novo aneurysm formation The incidence of de novo aneurysms after surgical clipping or endovascular
coiling is uncertain, in part because aneurysms may be missed at the time of initial hemorrhage [21,23]. As an
example, CTA was used to screen 495 patients who had had prior surgical clipping of a ruptured aneurysm at a
mean 8 years previously (range 4 to 14 years). In 87 patients (18 percent), at least one aneurysm was found at a
different location than the clip site [23]. Of these 87 patients, the original digital subtraction angiography (DSA) or
CTA was available for 51 patients (with 62 aneurysms on follow-up study). Comparison of the original and screening
studies revealed that 19 of 62 aneurysms (31 percent) were de novo, and 43 (69 percent) were visible in retrospect.
Other cohort studies also find that a significant percentage of new aneurysms are present on the original
angiogram, when it is available for expert review [2,22].
De novo aneurysm formation probably occurs at a low rate; in one case series the five-year cumulative incidence
after aneurysm coiling was 0.75 percent [24]. Other studies have reported annual incidence of de novo aneurysm
formation of 0.3 to 1.8 percent in patients who have had one aneurysm treated [6,21,25,26]. Multiple aneurysms,
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smoking, and female gender have been associated with de novo aneurysm formation in some studies [24].
Growth of pre-existing aneurysms Approximately 20 percent of patients with aneurysmal SAH have multiple
aneurysms. Depending on their size, location, and other factors, these may be treated at the same time as the
index (ruptured) aneurysm. However, smaller unruptured aneurysms and those less accessible to treatment may be
observed rather than repaired.
In one study, serial imaging studies were used to follow 87 patients with 111 unruptured aneurysms; 79 patients
had ruptured aneurysms clipped at start of followup [27]. Unruptured aneurysms increased in size by 1 mm in 45
percent of patients and by 3 mm in 36 percent. Cigarette smoking was a risk factor for 3 mm aneurysm growth.
Other follow-up studies in patients after SAH have also documented a significant rate of aneurysm growth in
untreated aneurysms [23]. Recurrent SAH occurred in 1.6 percent of patients per year and was significantly
predicted by aneurysm growth. Additional risk factors for aneurysm growth are larger aneurysm size, multiple
additional aneurysms, and female gender [24].
FOLLOW-UP EVALUATIONS There is no consensus on whether and how to screen for new or recurrent
aneurysms after SAH [4].
At least two decision models have been used to evaluate the utility of follow-up imaging studies:
In the first study, outcomes after SAH were modeled using expected outcome and complications rates
obtained from a literature review. It was assumed that patients had successful obliteration of all aneurysms
by surgical clipping or endovascular coiling after the index SAH [28]. Patients were screened with computed
tomographic angiography (CTA). The expected quality-adjusted life years was virtually the same (about 8.3
years) for no screening, screening once at five years, and screening every two years, regardless of the initial
type of treatment. Screening prevented new episodes of SAH, but the benefit was offset by the cost of
increased morbidity from diagnostic tests and preventive treatment. As an example, with screening every two
years after coiling, the expected rate of SAH decreased from 1.9 to 0.5 percent and mortality decreased
from 0.9 to 0.6 percent, but the disability rate increased from 0.5 to 1.9 percent due to complications from
angiography and retreatment.
In a second study, 610 patients with SAH were screened with CTA 2 to 18 years after surgical clipping, and
the results of screening were used as input for a decision analysis [22]. Screening every five years
(compared with no screening) prevented nearly half of the SAH recurrences, but life expectancy increased
only marginally, and these benefits were offset by a negative impact on quality of life and by increased
costs. Screening became cost-effective but did not increase quality of life in patients when the risks of
aneurysm formation and rupture were doubled, and screening was cost-effective and improved quality of life
in patients with a 4.5-fold increase in both risks. In addition, screening increased quality of life at acceptable
costs in patients with fear for a recurrence.
In the face of limited and conflicting data, it is our opinion that patients require comprehensive follow-up after SAH.
Extra vigilance is warranted for patients with risk factors for recurrent SAH and aneurysm regrowth, such as
incomplete occlusion at initial treatment, large aneurysm size, multiple aneurysms, hypertension, and cigarette
smoking.
For patients treated with endovascular coiling, we obtain immediate evaluation of the coil mass by angiography
during the procedure. Plain skull films typically provide excellent coil visualization and are obtained immediately
post procedure. Plain skull film screening is also obtained at two weeks, three months, and six months postprocedure. If the plain skull films reveal evidence of aneurysmal recanalization such as coil compaction, loosening,
or reorientation, DSA is obtained. In addition, we recommend DSA at three to six months for all patients who have
undergone coiling, as angiography remains the gold standard [13], although some data suggest that magnetic
resonance angiography may be sufficiently accurate for this purpose, it is probably to some extent center-specific
[29,30].
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For patients treated with surgical clipping of aneurysms, we obtain screening with magnetic resonance angiography
(MRA) or CTA at three and six months. Additional angiography is performed only if there are worrisome features on
the noninvasive studies.
Further follow-up imaging studies depend on the appearance and size of the treated and any other aneurysms, the
presence of risk factors for aneurysm recurrence, and the patients functional status and individual preferences.
It should be noted that coil artifacts may interfere with interpretation of CTA in patients treated with coiling, whereas
MRA interpretation may be impaired by large artifacts around clipped aneurysms [31,32]. Therefore, CTA is
preferred for assessment of patients with clipped aneurysms, and MRA is preferred for patients with coiled
aneurysms [33,34]. In one study of 60 patients with 74 coiled aneurysms followed with both angiography and MRA,
agreement between the two studies was good. In only 4 aneurysms was recanalization seen on DSA that was not
seen on MRA with the degree of angiographic recanalization in these patients considered too minor (<3 mm) to
indicate further treatment [35].
MANAGEMENT Treatment of a recurrent, previously-treated aneurysm may involve either endovascular coiling or
surgical clipping depending on the aneurysm morphology and may not be the same as the initial approach [3,22].
Retreatment is not benign. In one case series, 11 percent of recoiling procedures were associated with potentially
life-threatening or disabling events, while 2 of 12 repeated surgical procedures resulted in death [3]. Other treatment
options for recurrent aneurysm after endovascular treatment include a recoiling procedure with placement of a
covered stent in some cases [36]. Surgery can be used to treat a recurrent or incompletely occluded aneurysm
after coiling [37,38].
A decision to treat de novo aneurysms or enlarging pre-existing aneurysms uses the same considerations
employed for other unruptured aneurysms. (See "Unruptured intracranial aneurysms", section on 'Management of
unruptured aneurysms'.)
The severity of the functional and neurologic morbidity incurred during the index SAH is also a consideration in
determining whether intervention is likely to be of overall benefit to the patients quality of life.
SUMMARY AND RECOMMENDATIONS
Patients who have had an aneurysmal subarachnoid hemorrhage (SAH) have a small but enduring risk of a
recurrent aneurysmal rupture relative to the general population with a cumulative 10-year incidence as high
as 3 percent. (See 'Epidemiology' above.)
Recurrent SAH may result from recurrence of the treated aneurysm, rupture of another pre-existing
aneurysm in a patient with multiple aneurysms, or de novo aneurysm formation. (See 'Causes' above.)
Recurrence of the treated aneurysm occurs in 9 to 34 percent of endovascularly-treated aneurysms.
Incomplete occlusion and larger (>10 mm) aneurysm size are risk factors for recurrence.
Recurrence of a successfully surgically clipped aneurysm is relatively rare (<1 percent).
The incidence of de novo aneurysms after surgical clipping or endovascular coiling is uncertain, but
appears to occur in 0.3 to 1.8 percent of patients per year. The risk is higher in patients with multiple
aneurysms and those who smoke.
Growth of pre-existing unruptured aneurysms occurs in a significant number of patients. Smoking, larger
aneurysm size, multiple additional aneurysms, and female gender are risk factors.
The frequency and type of neuroimaging follow-up depends on many factors including the treatment
(endovascular versus surgery) of the index aneurysm, the presence of risk factors for recurrent aneurysmal
formation, the number and size of any additional aneurysms, and the neurologic status and preferences of
the patient. Most patients who have undergone endovascular treatment of their aneurysm should undergo
angiography approximately six months after the initial repair. We typically obtain computed tomography
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angiography (CTA) at three to six months after surgical clipping of a ruptured aneurysm. (See 'Follow-up
evaluations' above.)

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Topic 16257 Version 5.0

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Disclosures
Disclosures: Robert J Singer, MD Nothing to disclose. Christopher S Ogilvy, MD Nothing to disclose. Guy Rordorf, MD Nothing to
disclose. Jose Biller, MD, FACP, FAAN, FAHA Nothing to disclose. Janet L Wilterdink, MD Employee of UpToDate, Inc.
Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vetting through
a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced
content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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