Modern Management of Brain Aneurysms
and Vascular Malformations
by Gregory J. Zipfel, MD
It has become apparent
that a multidisciplinary
approach is mandated
for best management of
cerebrovascular patients.
Gregory J. Zipfel, MD, 1-year MSMA
member, is Assistant Professor of
Neurological Surgery in the Departments
of Neurological Surgery and Neurology
at Washington University in St. Louis.
Contact: [email protected]
Abstract
The
management
of
brain aneurysms and vascular
malformations has evolved rapidly
in recent years. More of these
lesions are being diagnosed due to
higher fidelity imaging, treatment
has become more refined and
often less invasive, and patients
have become more integrated in
their own care due to advances in
information technology. This article
reviews the clinical characteristics
and therapeutic options for
patients harboring these lesions,
with a particular focus on recent
advances in the field.
Introduction
Over the past decade, substantial
improvements in natural history,
diagnosis, and intervention have
occurred for numerous cerebrovascular
diseases including brain aneurysms
and vascular malformations. Specific
examples include more robust natural
history data, enhanced sensitivity and
specificity of noninvasive imaging
modalities, improvement and increased
utilization of less invasive therapeutic
modalities including endovascular
therapy and Gamma Knife radiosurgery,
and refinements in surgical technique.
This article highlights recent advances
and provides a detailed review of
best practice for the care of patients
harboring aneurysms, cavernous
malformations, and arteriovenous
malformations (AVMs) of the brain.
Aneurysms
Epidemiology
The prevalence of brain aneurysms
in the general population is 1-3%;
however, certain individuals are
at increased risk1. Female gender
and family history of aneurysm or
subarachnoid hemorrhage (SAH)
are known risk factors. Autosomal
dominant polycystic kidney disease
(ADPKD) is also associated with
increased aneurysm prevalence. Active
cigarette smoking not only increases
the risk for aneurysm formation, but
also increases the probability that a
known aneurysm will rupture. Finally,
presence of an AVM markedly increases
the risk of aneurysm formation, owing
to the hemodynamic stress associated
with these high flow lesions.
Diagnosis
Unruptured aneurysms most
commonly present incidentally, while a
distinct minority present with aneurysm
specific symptoms. Examples of the
latter include aneurysms arising near
the optic nerve presenting with visual
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deficits, aneurysms in close proximity to
the oculomotor nerve presenting with
diplopia or ptosis, and aneurysms having
intraluminal thrombus presenting with
ischemic stroke. Ruptured aneurysms,
on the other hand, most commonly
present with symptoms referable
to SAH. Classically, these include
a “thunderclap” headache, nausea,
vomiting, neck stiffness, decreased
mental status, and/or focal neurological
deficits.
The radiographic study of choice
for evaluation of a patient with
suspected SAH is head computed
tomography (CT) (Figure 1A). The
sensitivity of head CT is very high within
the first 24 hours; however, sensitivity
drops quickly when patients present in
delayed fashion. Lumbar puncture is
often used when head CT is negative or
equivocal. Results consistent with SAH
include increased red blood cell count
in serial tubes as well as xanthochromia
(i.e. yellowish discoloration due
to red blood cell breakdown).
Catheter cerebral angiography has
for decades been considered the gold
standard for aneurysm detection
and characterization (Figures 1B
and C).
However, noninvasive
imaging techniques such as computed
tomographic angiography (CTA) and
magnetic resonance angiography
(MRA) have vastly improved in recent
years and have begun to approach the
sensitivity and specificity of catheterbased angiography, especially for lesions
>3mm in size.
Natural History
Figures 1
Subarachnoid hemorrhage and cerebral
aneurysm.
Figure 1A
Non-contrast head CT demonstrating
acute subarachnoid blood
(hyperdensity) within the basal cisterns
and sylvian fissures.
Figure 1B
Two-dimensional catheter
angiogram revealing
a large anterior
communicating artery
aneurysm.
Figure 1C
Three-dimensional catheter
angiogram demonstrating
the detail architecture
of a large anterior
communicating artery
aneurysm including two
views of the aneurysm neck
and arterial branches.
Unruptured Aneurysms
The landmark International Study
of Unruptured Intracranial Aneurysms
(ISUIA)2 was a large scale multicenter
observational study aimed at assessing
hemorrhage risk of unruptured
aneurysms.
Several important
observations were noted. First, critical
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Figures 2
unruptured aneurysms appeared less
than that previously reported. Though
ISUIA was subject to a strong selection
bias as well as other study weaknesses,
it remains the most robust prospective
natural history data available to date.
Treatment options for cerebral aneurysms.
Ruptured Aneurysms
While hemorrhage risk of
unruptured
aneurysms
remains
incompletely
defined,
bleeding
risk of ruptured aneurysms is well
documented, with most studies
reporting rebleeding rates of 40% in the
first four weeks after SAH3. Moreover,
though the morbidity and mortality
associated with initial SAH is high (50%
of patients die and 50% of survivors
suffer long-term cognitive deficits), the
consequences of re-hemorrhage are
even greater (80% of patients die or
remain severely disabled)3.
Figure 2A
Surgical clipping. Intra-operative photograph of complex internal carotid artery
aneurysm obliterated by two fenestrated aneurysm clips.
Figure 2B
Endovascular coiling. Intra-procedural photograph demonstrating deployment of
platinum metal coils via microcatheter within large basilar artery aneurysm.
aneurysm size associated with increasing
hemorrhage risk was found to be 7 mm.
Second, aneurysm location significantly
affected hemorrhage risk, as lesions
arising from the anterior cerebral,
middle cerebral and internal carotid
arteries carried lower risk compared to
lesions arising from the vertebral, basilar,
and posterior communicating arteries.
Third, patients with history of SAH were
at increased risk of aneurysm rupture.
Fourth, the overall hemorrhage risk of
Overall Management
Much of SAH management is
focused on preventing or managing one
of the following complications:
1) hydrocephalus
2) aneurysm re-bleeding
3) seizures and
4) cerebral vasospasm.
Regarding hydrocephalus, this
is a very common complication that
occurs within hours of ictus. Acute
treatment is mandatory and involves
insertion of a ventriculostomy for
drainage of cerebrospinal fluid (CSF).
As blood within the subarachnoid space
dissipates over time, many patients can
be weaned from the ventriculostomy
while others will require permanent
CSF shunting. Regarding aneurysm
re-bleeding, the risk is very high as
described above. In decades past
aneurysm treatment was often delayed;
however, modern management includes
aneurysm obliteration within 24-48
hours of presentation. Early aneurysm
treatment not only reduces re-bleeding
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rates, but also allows for aggressive
hemodynamic therapy for cerebral
vasospasm.
Seizures are a fairly common
event after SAH and are to be avoided;
particularly prior to aneurysm
treatment when seizure activity and
its attendant rise in blood pressure
could promote aneurysm re-rupture.
Antiepileptic drugs are prescribed in all
patients upon admission and continued
for at least several days. Longer term
antiepileptic treatment is only required
in those deemed at particular risk for
ongoing seizures.
Cerebral vasospasm is the greatest
source of secondary neurological injury
following SAH. It is defined as delayed
narrowing of large cerebral arteries
in response to the initial SAH. Its
incidence is high, with angiographic
evidence of vasospasm occurring in 6070% of SAH patients and vasospasminduced ischemic neurological deficits
occurring in 30-40% of SAH patients4.
Treatment for cerebral vasospasm is
multifaceted3. First, all patients are
prophylactically placed on a calcium
channel blocker (Nimodipine), which is
proven to reduce secondary neurologic
deficits due to vasospasm. Second,
patients who develop vasospasminduced symptoms are treated with
hemodynamic therapy (i.e. induced
hypervolemia and/or hypertension)
as well as select use of endovascular
therapy, i.e. intra-arterial vasodilators
and/or angioplasty. Despite these
measures, vasospasm-induced brain
injury remains a significant source of
neurological morbidity after SAH.
Aneurysm Treatment
Direct surgical approaches for
aneurysm obliteration have been the
mainstay of treatment since the late
1960s and early 1970s, and involves
placement of a titanium metal clip
across the neck of the aneurysm
(Figure 2B). More recently, the utility
and efficacy of endovascular therapy
has gained widespread acceptance.
Endovascular treatment involves
insertion of platinum metal coils via
a microcatheter to achieve aneurysm
obliteration (Figure 2C). Adjuvant
use of balloon and stent technology
to assist with coil embolization has
further broadened the applicability of
endovascular treatment.
Ruptured Aneurysms
Due to the very high incidence of rebleeding after SAH and the acceptable
risks associated with surgical and
endovascular aneurysm repair, the vast
majority of patients with SAH should
undergo aneurysm treatment in the
acute period. Withholding aneurysm
treatment is typically reserved only for
those patients with very poor prognosis
(e.g. patients who are elderly, medically
infirm, and/or in very poor neurological
condition). Importantly, a trial period
of CSF drainage via ventriculostomy
should be provided in the vast majority
of patients, as many experience
dramatic improvement in their
neurological status and subsequently
warrant aneurysm treatment.
In regards to choice between
surgery and endovascular therapy,
many factors must be considered.
Size, configuration, and location of the
aneurysm are critical. Several patient
factors are also important, including
patient age, medical co-morbidities,
presenting neurological condition, and
patient preference. Local availability and
depth of experience of microvascular
surgery and endovascular therapy
can also affect treatment choice.
Finally, results from the International
Subarachnoid Aneurysm Trial (ISAT)
should be considered.
ISAT5 was a landmark randomized
controlled trial (RCT) designed
to evaluate safety and efficacy of
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surgical versus endovascular therapy
for ruptured aneurysms. It included
patients with recent SAH where
the treating physicians felt that the
offending aneurysm was equally
amenable to surgical or endovascular
therapy – a scenario termed “clinical
equipoise.” Patients were randomized
to surgical or endovascular therapy.
Importantly, enrolled patients in this
study represented only 22% of those
patients having ruptured aneurysms
at the participating institutions,
suggesting that superiority of one
treatment over the other was present
in the majority of patients. Results
from ISAT found an overall superior
outcome at one year for patients treated
with endovascular vs. surgical therapy
– a benefit that occurred despite
increased chance of re-treatment and
increased incidence of re-bleeding in
the endovascular patients. This result
favoring endovascular therapy has had
a major impact on practice patterns
for ruptured aneurysms, with many
institutions experiencing an increase in
endovascular aneurysm treatment after
its publication.
Unruptured Aneurysms
By the early 1990s, a general
consensus in the neurologic community
had been achieved regarding best
practice for unruptured aneurysms –
that is, these lesions were felt to be quite
dangerous and should be repaired by
surgical means in most patients. Since
that time, two events have significantly
challenged this treatment paradigm.
One, new data regarding the natural
history of unruptured aneurysms
became available. Two, development
and widespread application of
endovascular therapy dramatically
altered aneurysm treatment paradigms.
Regarding the former, data from ISUIA2
suggested that annual hemorrhage risk
for unruptured aneurysms, particularly
Figure 3
Cavernous malformation.
T2-weighted MRI demonstrating
cavernous malformation in
the right parietal lobe. Note
characteristic hypointense
hemosiderin ring surrounding the
lesion.
those less than 7 mm in size, was less
than previously reported. Regarding
the latter, the availability and excellent
safety profile of endovascular therapy
led to a marked increase in its use for
unruptured aneurysms.
However, no RCTs comparing
surgery vs. endovascular therapy
for unruptured aneurysms have
been reported to date. Therefore at
present, no direct evidence to suggest
superiority of one treatment modality
over the other exists for unruptured
lesions. Decisions regarding choice
of treatment modality consequently
remain at the discretion of the treating
physician, and are based on thorough
evaluation of multiple factors that might
affect hemorrhage and procedural risk,
including aneurysm characteristics,
patient factors, and issues of local
surgical and endovascular expertise.
Cavernous Malformations
Epidemiology, Diagnosis, and Natural
History
Cavernous malformations are
discrete, well-described multilobulated
lesions characterized by abnormally
enlarged capillary cavities without
intervening brain parenchyma.
Their prevalence in the general
population has been estimated
as 0.1-0.5%6. They are best
identified on MRI where they
have a well-defined lobulated
appearance and a characteristic
rim of signal hypointensity on
T2 weighted images (Figure 3).
Cavernous malformations
most commonly present with
cerebral hemorrhage, seizure,
or as an incidental finding.
When they bleed, the extent of
hemorrhage is typically smaller
and the neurological deficits
less severe than that associated
with aneurysms or AVMs. The
annual hemorrhage risk of
a previously unruptured cavernous
malformation is thought to be 0.5-1%
per year, while the annual hemorrhage
risk of a recently ruptured cavernous
malformation is thought to be 4-5%
per year for several years7.
Treatment
Therapeutic options include
expectant management, antiepileptic
therapy, surgical excision, and in rare
cases Gamma Knife radiosurgery. Patients
with incidental lesions are typically
treated with expectant management,
owing to the low annualized risk of
debilitating hemorrhage.
Patients
presenting with seizures but without
hemorrhage are also commonly
managed without surgical intervention.
These patients are treated with
antiepileptic medications and if seizures
are well controlled, no further therapy
is required. For those wishing to avoid
long-term antiepileptic therapy and
having a surgically accessible cavernous
malformation, lesion resection can be
considered.
When a cavernous malformation
presents with hemorrhage and is in
a surgically accessible region (e.g.
cerebral or cerebellar cortex), lesion
resection is often recommended due
to the relatively high risk of recurrent
bleeding and the generally low risk
associated with surgery. Because the
neurological deficits associated with
cavernous malformation bleeding
are often non-disabling, expectant
management is also reasonable. When
surgically accessible lesions hemorrhage
on multiple occasions, however, lesion
resection is usually pursued.
When a cavernous malformation
presents with hemorrhage but is in a
surgically difficult to access or high risk
region (e.g. basal ganglia or brainstem),
lesion resection is often not pursued,
at least initially. This is due to the
significant risk associated with cavernous
malformation removal from these brain
regions. However, because deep seated
lesions are associated with particularly
high risk for recurrent hemorrhage,
some advocate resection for select
deep-seated lesions even in patients
who have suffered a single hemorrhage.
When deep-seated lesions hemorrhage
on multiple occasions, even greater
consideration for surgical intervention
is given.
Finally, Gamma Knife radiosurgery
has been utilized by some practitioners
as a means for treating cavernous
malformations. Evidence supporting
the efficacy of this approach, however,
is not robust. If pursued at all, Gamma
Knife radiosurgery is only indicated in
select cases where patients have suffered
multiple hemorrhages and harbor a
cavernous malformation that does not
permit surgical removal.
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Figures 4
Arteriovenous malformation.
Figure 4A
T2-weighted MRI demonstrating a
tangle of vascular flow voids in the
right frontal lobe, consistent with an
arteriovenous malformation.
Figure 4B
Catheter angiogram demonstrating
a high-flow right frontal
arteriovenous malformation.
Arteriovenous
Malformations
Epidemiology, diagnosis, and natural
history
AVMs are congenital lesions
composed of a nidus of thin walled
dysplastic vessels that permit shunting
of high pressure arterialized blood from
dilated feeding arteries to thin-walled
draining veins. Most AVMs are well
demonstrated on CT and MRI (Figure
4), though small lesions are sometimes
difficult to identify. All AVMs require
formal catheter angiography to fully
assess their architecture and to examine
for associated aneurysms. Based on
several autopsy studies, the prevalence
of AVMs appears to be 1-4%8.
AVMs most commonly present
with cerebral hemorrhage, which is
associated with 10-20% morbidity
and 10-30% mortality8. Seizure is the
second most frequent presentation.
This is most common for superficial
AVMs and in particular those residing
within the temporal lobe. Other modes
of presentation include headache,
progressive neurological decline, and
as an incidental finding.
The natural history of AVMs,
in contrast to that of aneurysms, is
well defined, with several studies
demonstrating a 2-4% annual
hemorrhage risk for unruptured
lesions. This risk appears to be
temporarily
higher
following
AVM rupture, with most studies
documenting 6% annual hemorrhage
risk in the first post-hemorrhage year
followed thereafter by a 2-4% annual
hemorrhage risk8.
Treatment
Management options for AVMs
include observation, craniotomy for
resection, Gamma Knife radiosurgery,
endovascular
embolization,
or
multimodality treatment. The latter
may include a combination of surgery,
radiosurgery and/or embolization
depending on the complexity and
clinical scenario of a given AVM.
Surgical resection for AVMs has
been a mainstay of treatment since the
1960s. It has the advantage of acutely
eliminating risk of rupture and may also
improve seizure control for those with
history of seizure. Its disadvantages are
that it is invasive, that it can at times
carry significant risk, and that it entails
a several-day hospitalization and a
several-week overall period of recovery.
Radiosurgery involves a one-time
delivery of stereotactically targeted
high-dose radiation to the AVM with
minimization of radiation to the
surrounding brain. It has the advantage
of being an outpatient procedure
418 w September/October 2008 w 105:5 Missouri Medicine
with a very short period of recovery
as well as an attractive procedural
risk profile. Its disadvantages include
gradual obliteration of the AVM nidus
over 1-3 years during which the risk
of hemorrhage remains, higher risk
for incomplete AVM obliteration,
and limitation to predominantly
smaller lesions (i.e. diameter ≤ 3
cm). Endovascular therapy involves
manipulation of a microcatheter into the
AVM nidus, followed by administration
of an embolic agent designed to reduce
blood flow. Its advantages include a
less invasive procedure, a brief period
of hospitalization, and a relative
short period of overall recovery. Its
disadvantages are that endovascular
therapy can at times carry significant
risk and that it uncommonly leads
to complete AVM obliteration. Due
to the latter, endovascular treatment
is infrequently used as a stand alone
procedure, but more commonly
employed as a preoperative adjunct to
improve the overall safety of surgical
resection.
Patient factors to be considered
during therapeutic decision making
include: patient age, medical comorbidities (both of which make
surgical and endovascular therapy less
attractive), and patient preference.
Certain AVM characteristics must also
be considered, the most important of
which are size and location. For most
small and moderate sized AVMs that
are located apart from eloquent brain
regions, surgical resection is generally
considered treatment of choice. This
relates to its very high chance of
complete AVM obliteration, acute
elimination of bleeding risk, and
a generally attractive procedural
risk profile. For lesions ≤ 3cm in
diameter and located within eloquent
brain, Gamma Knife radiosurgery is
typically best. This relates to its high
chance of AVM cure and superior
procedural risk profile. When AVMs
fall outside these treatment categories,
controversy exists regarding best
practice. Many believe such lesions
are best left untreated, though these
patients remain at substantial risk for
hemorrhage. Others have reported
relative success via multimodal
therapeutic approaches that typically
involve staged radiosurgery or
staged embolization followed by
radiosurgery. The majority agrees
that surgical intervention for most of
the more formidable AVMs is to be
avoided.
Conclusion
Over the past 10-15 years, great
advancement in the management of
patients with cerebrovascular disease has
been achieved by refinements in natural
history, introduction of new and less
invasive therapeutic procedures, and
advancements in surgical technique.
It has also become apparent that a
multidisciplinary approach is mandated
for best management of cerebrovascular
patients, as an ever-growing breadth
of expertise is required in order to
deliver optimal care. This entails a
collaborative spirit between numerous
specialists including cerebrovascular
surgeons, endovascular specialists,
vascular neurologists, neurointensivists,
radiosurgical and radiation therapists,
neuroradiologists, as well as many other
physician and non-physician caregivers.
It is anticipated that further advances in
the care of cerebrovascular patients will
continue to occur over time, as novel
and often less invasive technologies
become further refined and validated.
References
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3rd, et al. Unruptured intracranial aneurysms:
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2003;362(9378):103-10.
3. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid
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neurosurgical clipping versus endovascular coiling in
2143 patients with ruptured intracranial aneurysms:
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6. Labauge P, Denier C, Bergametti F, TournierLasserve E. Genetics of cavernous angiomas. Lancet
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natural history of cerebral cavernous malformations.
J Neurosurg 1995;83(5):820-4.
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Disclosure
None reported.
MM
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