Late recurrence of subarachnoid hemorrhage and intracranial aneurysms

Authors:
Robert J Singer, MD
Christopher S Ogilvy, MD
Guy Rordorf, MD
Section Editor:
Jose Biller, MD, FACP, FAAN, FAHA
Deputy Editor:
Janet L Wilterdink, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Jul 2017. | 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 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,
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 post-procedure. 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].

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 angiography (CTA) at three to six months after surgical clipping of a
ruptured aneurysm. (See 'Follow-up evaluations' above.)

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