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CEREBRAL MYCOTIC
ANEURYSMS
ABSTRACT
BACKGROUND AND PURPOSE: Cerebral mycotic aneurysms are a rare and
deadly type of aneurysm that have no definitive treatment
guidelines. Our purpose was to retrospectively review known or
suspected cases of CMA in order to identify patient populations that
may be associated with higher morbidity and mortality. We hope that
the identification of patients with these risk factors will lead to
early stratification upon presentation, and more urgent treatment of
their CMAs. We also hoped to identify any benefit or complication
that was specific to either the endovascular or neurosurgical repair
of CMAs.
MATERIALS AND METHODS: A retrospective multi-institutional
study was performed examining cases of CMA during a 15-year period.
Patients were considered strongly immunocompromised if there were
long-term severely immunocompromised states: AIDS, chemotherapy, or
steroid immunosuppression. Patients were excluded if angiographic
findings suggested an alternative diagnosis or if an infectious
etiology was unknown. Antibiotics were considered “noninvasive
treatment.” Endovascular and neurosurgical repair were considered
“invasive treatment.” Data were recorded by reviewing electronic
medical records and imaging reports.
RESULTS: Twenty-six patients with 40 CMAs were included.
Three patients were considered strongly immunocompromised and
presented with 4 CMAs, which demonstrated larger average size and
more rapid growth; 3 of these patients’ aneurysms were treated
invasively in the acute period, with the one that was not ruptured
causing death. Technical success (aneurysm occlusion without rupture
or recanalization) and clinical success (no neurologic complication
attributable to the intervention) were obtained equally
endovascularly and neurosurgically. Clipping was aborted in favor of
coiling for 1 patient. Anticoagulation needed reversal before 2
patients underwent craniotomy for clipping after valve replacement.
For CMAs treated with antibiotics alone with angiographic follow-up
(n 11), initial aneurysm size was unrelated to persistence and 64%
completely regressed.
CONCLUSIONS: We recommend initial invasive treatment for CMAs
in strongly immunocompromised patients. Testing for underlying
immunocompromised states is warranted in patients with CMAs.
Endovascular treatment is favored over neurosurgical treatment in
patients requiring acute cardiac valve repair due to delays with
anticoagulation reversal.
ABBREVIATIONS: CMA cerebral
mycotic aneurysms; ECA external carotid artery; ICP intracranial
pressure; IE infective endocarditis; IPH intraparenchymal
hemorrhage.
Important Notice:
This article is based upon
the data acquired from Allen L.M. et al from the AJNR Published
11-October-2012.
Cerebral mycotic aneurysms or infectious intracranial aneurysms
represent less than 5% of all intracerebral aneurysms.1 They are
most commonly seen in patients with septicemia and HIV/AIDS and are
a particularly well-known complication of infective endocarditis.
Intravenous drug abuse and “relative immunocompromised” states such
as diabetes are becoming more commonly associated with CMAs.2-4
Studies report 1%–10% of patients with IE have CMAs; and of patients
with CMAs, approximately 65% have IE.3,5 In “strongly
immunocompromised” patients, CMAs are prone to more rapid growth and
rupture.6-8 If there is direct meningeal extension of infection,
CMAs are often located more proximally than their usual location at
distal branch points. In addition, CMAs from atypical infections,
especially fungal infections, are particularly lethal.6-8
Many believe that endovascular repair should be the treatment of
choice for CMAs if the patient is to have valve replacement for IE.5
If the patient had recent valve replacement, craniotomy may be
contraindicated due to anticoagulation for either mechanical or
bioprosthetic valves. If craniotomy is performed before valve
replacement, there is greater risk for perioperative heart failure
compared with endovascular treatment. Endovascular coiling has been
successfully performed as early as 1 day before valve
replacement.9,10 If there are anticoagulation or heart failure
concerns, endovascular repair is thought to be a more prudent option
than neurosurgical treatment, though, to our knowledge, there are no
current prospective data supporting this.
A review of the relevant literature shows no widely accepted
guidelines for treating CMAs. Several authors recommend only
neurosurgical treatment for ruptured CMAs with intraparenchymal
hemorrhage and mass effect.11-13 There are no prospective randomized
trials comparing endovascular and neurosurgical repair. Endovascular
repair is becoming more popular and has been recommended by some to
be the treatment of choice.14 Prior opinion was that the
introduction of foreign material into infected vasculature increases
infection and rupture rates.15 However, many reports, including a
recent literature review that examined 287 cases of CMAs, 46 of
which were treated endovascularly, found no postprocedural
infections or abscesses for the endovascularly treated patients.5
There have only been 3 reported cases of infection after CMA
coiling, and there has also been successful coiling in the setting
of active bacteremia.16
We retrospectively reviewed known or suspected cases of CMA to
better improve management, particularly for strongly
immunocompromised patients. Technical success for neurosurgical and
endovascular repair was analyzed as well as patient risk factors
that may lead to increased morbidity and mortality.
MATERIALS AND METHODS
Multi-institutional review board
approval was obtained, and a waiver of informed consent was granted
for this Health Insurance Portability and Accountability
Act-compliant study. A retrospective nonrandomized study was
performed at the University of California, Irvine Medical Center,
Department of Radiologic Sciences (2 patients); Mallinckrodt
Institute of Radiology, Washington University (13 patients); and the
University of Washington Medical Center, Department of Radiology (11
patients).
All known or suspected CMA cases were reviewed to include adult
patients. Patients were excluded if there was a lack of angiographic
findings suggesting CMA or a lack of infectious etiology or if a
detailed angiographic study, either catheter angiography or CT
angiography, was not performed.
For the purpose of this study, intravenous antibiotics were
considered “noninvasive” treatment and endovascular and
neurosurgical repair were considered “invasive” treatments. We
defined “acute” valve replacement as that occurring within the first
6 weeks after the IV antibiotic initiation. Patients with long-term
severe immunosuppression (i.e., those with AIDS, those receiving
chemotherapy, or those undergoing steroid immunosuppression) were
considered strongly immunocompromised.
Patients with conditions such as chronic renal failure, diabetes,
and chronic alcohol abuse were considered “relatively
immunocompromised.”
The following parameters were recorded after review: patient age,
sex, presenting symptoms, initial imaging findings, comorbidities,
presence of IE, cardiac valve-replacement surgery, timing of valve
surgery, likely source of infection, status of blood cultures and IV
antibiotic administration, number of CMAs, location of CMAs, size of
CMAs, record of invasive intervention, technical and clinical
success of the intervention, patient morbidity and mortality, and
aneurysm size on follow-up imaging. For aneurysm size, the largest
dimension was used. In patients whose aneurysm size varied during
the course of treatment, the largest measured size was used.
Technical and clinical success of the intervention was defined as
successful exclusion of the aneurysm without recanalization or
repeat bleed, no intraoperative or immediate
postoperative rupture, and absence of clinical complications in the
immediate postoperative period attributable to the intervention.
RESULTS
Patient Parameters
All patients received intravenous antibiotics. Patient 4 had a CTA
but was unable to have a catheter angiogram before he died. Limited
information was available about initial symptoms in patients 4, 15,
and 26. Patient 26 had a remote history of IE with subsequent valve
replacement and presented with an incidental CMA years later; data
regarding his initial presentation were limited.
Follow-up information was not available for patient 15. Information
on the sizes of the aneurysm of patient 10 and 1 aneurysm in patient
25 was unavailable. The average patient age was 45 years (range, 26
–77 years). Most patients were men (18/26, 69%). The initial
presenting symptom was known in 81%. The most common symptoms were
headache (13/21, 62%), focal neurologic deficit (9/21, 43%), and
fever (4/21, 19%). Initial imaging findings included subarachnoid
hemorrhage (10/25, 40%), septic infarct (9/25, 36%), and IPH (8/25,
32%). Sixty percent (15/25) of patients had ruptured CMAs, and most
had IE (19/26, 73%). The most common pathogen from blood cultures
was Staphylococcus aureus, followed by Streptococcus species. Common
risk factors were intravenous drug abuse, poor dental hygiene, or a
recent dental procedure. Three patients were considered strongly
immunocompromised on the basis of the long duration of a severely
immunocompromised state: patient 7 from AIDS, patient 22 from
chronic steroid use for Crohn disease, and patient 24 from
chemotherapy for advanced multiple myeloma.
Patients Requiring Cardiac
Valve Repair
Ten of the 26 (38%) patients needed cardiac valve replacement
from IE, which represented 52% (10/19) of all patients with IE.
Five patients underwent acute valve replacement, and patients
10 and 22 needed anticoagulation reversal, which delayed
craniotomy.
Aneurysm Parameters
Forty CMAs were identified among 26 patients. The most common
location was the MCA and its branches (31/40, 78%). The
next most common locations were the anterior cerebral artery
and ICA. Aneurysm size was available for 95% (38/40) and ranged
from 1 to 15 mm (mean, 5 mm; median, 4 mm). Aneurysms were
multiple in 38% (10/26).
There was an equal incidence of endovascular (n 9) and
neurosurgical repair (n 9). Seven aneurysms were treated with
coiling (1 with a stent scaffold), 2 with gluing, 5 with clipping, 1
with radial artery bypass, 2 with ECA-ICA bypass, and 1 with
coagulation.
Antibiotic Treatment Alone
Of the 22 CMAs treated with antibiotics alone, 50% had angiographic
follow-up. The other half did not have follow-up due
to patient death. Follow-up ranged from 1 month to 4 years,
and 64% (n 7) completely resolved, 18% (2/11) decreased in size, and
18% (2/11) were stable. CMAs in 4 patients (patients 5, 7, 9, and 22)
enlarged
during their treatment; patients 7 and 22 were strongly
immunocompromised.
Strongly Immunocompromised Patients.
Patients 7, 22, and 24 were strongly immunocompromised and
were classified as such due to a long-term severely
immunocompromised
state. These patients presented with the largest and
most rapidly growing CMAs. Average aneurysm size was 11 mm
(n 4).
Patient 7 had AIDS and coccidioidal meningitis. Initially he
had a right 8-mm M1 MCA aneurysm, which was successfully
coiled with stent scaffolding. Within 7 days between angiograms,
he developed a 13-mm anterior communicating artery aneurysm. This was not treated invasively and ruptured, causing his
death.
Patient 22, with Crohn disease and chronic steroid
immunosuppression,
presented with a multilobed left M2 MCA aneurysm,
which grew from 6 to 14 mm within 13 days. He presented
with a large septic infarct and was treated initially by clipping,
which was aborted after brain herniation out of the craniotomy
site secondary to increased ICP. This was successfully coiled.
Patient 24 was on chemotherapy for multiple myeloma and
had invasive aspergillosis of the orbit and sinuses and developed
an irregular 13-mm left cavernous ICA aneurysm, which was
successfully
coiled.
Five patients exhibited states of relative immunocompromise,
which included chronic renal failure, diabetes, and chronic alcohol
abuse. The number of relatively immunocompromised patients
in the study is likely greater, given that information on
chronic medical conditions in several patients was unobtainable
either due to lack of prior medical care or unobtainable patient
history.
DISCUSSION
The study of Allen L.M. et al. is concurrent with most reported prior demographics
with an average patient age range from 35 to 55 years; some reported
a male predominance and others found no sex predilection.5
Their average patient age was 45 years, and they found a slight
male predominance (69%). Their most common initial imaging
findings were SAH, septic infarct, and IPH. They found septic infarct
to be more common than IPH and focal neurologic deficit to
be a more common initial symptom than fever. Prior studies reported
SAH and IPH to be the most common imaging findings
and headache followed by fever as the most common presenting
symptoms.5 Current literature reports the MCA as the most common
location for CMAs in 50%–70% of patients.3,5 Similarly, they
found that 78% of the CMAs were located in the MCA. They found
CMAs to be multiple in 38% of patients, and this is close to prior
reports of approximately 25%.2,3
Allen et.al findings are consistent with prior literature that states that
both the lethality and size of CMAs during treatment are highly
variable and nearly impossible to predict. A study of 18 patients
with CMAs on antibiotics with a 6-week angiographic follow-up
reported complete resolution in approximately 30%; both enlargement
and decreasing size were seen in approximately 20%,
and about 30% remained stable.2 A second study reported CMAs
(10/20, 50%) that either resolved or disappeared and 10/20 (50%)
demonstrated no change or enlargement while the patient was on
antibiotic therapy.17 A third study found that approximately 30%
of CMAs resolved on antibiotics alone, about 20% decreased, 15%
were unchanged, and about 20% increased in size.5 Our higher
rate of clearance (64%, n 7) for patients on antibiotics than the
reported 30% average may be due to longer angiographic follow-up;
4 of 11 CMAs had follow-up of 1 year.
When and How to Treat
Some recommend angiography in all patients with IE who present
with a focal neurologic deficit to assess the possibility of CMA;
and if one is found, they recommend initial invasive treatment.
Others may invasively treat only ruptured CMAs. It remains
indeterminate
and is currently institution- and clinician-dependent as to which
approach should be used. Most CMAs (60%) in Allen et. al.
study were ruptured. The rupture rate of CMAs has been debated
with some reporting rates from 2% to 10%.18-20 Others report a
rate of nearly 80%.11,12,21 The sources reporting the higher rate
conclude that most clinically presenting CMAs are ruptured. Septic infarct is a more likely cause of neurologic deficit in a
patient
with IE than CMA. Several authors think that compared with
noninfectious cerebral aneurysms, CMA rupture rates are both
higher and do not increase with size; some think that often the
smaller aneurysms may be more likely to rupture. In addition,
even if the aneurysm is decreasing in size while the patient is on
antibiotics, rupture rates do not decrease.1,5,12,13 There have been
no formal studies correlating initial CMA size with persistence.
Although the number of aneurysms treated with antibiotics alone
that had angiographic follow-up in Allen et. al. study was small (n 11),
initial size appeared unrelated to persistence; the largest of these
CMAs completely resolved. If we considered mortality-based
outcomes for his 26 patients, 10 received antibiotics alone
and 4/10 (40%) died. Of the 16 who received some type of
intervention,
2/16 (13%) died; one of these deaths was due to complications
from a secondary disease state.
We agree with prior recommendations that a cerebral angiogram
is warranted in patients with IE who demonstrate a focal neurologic
deficit or mental status change. If a CMA is found, serial
angiograms
should be performed to assess stability.4 Because 5 of Allen et. al. patients
underwent acute cardiac valve-replacement surgery, 2 requiring
anticoagulation
reversal which delayed craniotomy, it is found that endovascular
repair to be the treatment of choice for
patients requiring acute valve replacement.
Although no complications were encountered
with endovascular or neurosurgical
repair, clipping had to be aborted in
favor of coiling in 1 patient due to craniotomy
complications from increased ICP.
Endovascular treatment of CMAs has its
own difficulties secondary to vessel wall friability,
which can lead to intraprocedural
wall rupture, the often irregular shape and
wide neck, and their often peripheral location.
Coiling is the most popular endovascular
option, and this was the most common
intervention in Allen et. al. study (n 7),
followed by clipping (n 5). For distal
MCAs, injectable polymers may be more
likely to cause infarction than coils when a
large arterial territory is treated, though both glue and Onyx (ev3,
Irvine, California) have been successfully used. Pretreatment Wada
testing may be necessary.14,22
Neurosurgical options include clipping, ICA-ECA bypass, excision
with vessel grafting, and coagulation. Cerebral mycotic aneurysms
from meningitis have been successfully excised surgically
but are often difficult to access postcraniotomy due to their often
more central location. However, there are 2 reported successful
cases of ICA-ECA bypass grafting for proximal CMAs.23 Two patients
in Allen et al. study were successfully treated by this method.
Immunocompromised Patients
The 3 strongly immunocompromised patients in Allen et al. study demonstrated
larger more rapidly growing aneurysms. The average aneurysm
size was 11mm (n 4)for these patients, compared with 5mm
(n 34) in the other patients. Three of the aneurysms in strongly
immunocompromised patients were successfully coiled in the acute
period without complications. The 1 aneurysm in patient 7 that was
not invasively treated ruptured, leading to his death. The
development
in patient 7 of a 13-mm anterior communicating artery aneurysm
in 7 days is very similar to a case by Minnerup et al,8 who
reported development of a large basilar artery CMA within 4 days in
an immunocompromised patient with bacterial meningitis. Patient
24, with invasive aspergillosis, developed a large 13-mm cavernous
ICA aneurysm. Similar findings are reported in the case of an
immunocompromised
patient who developed a large cavernous ICA aneurysm
secondary to invasive aspergillosis, which was treated successfully
with coiling and balloon embolization but then expanded
distally to involve the supraclinoid ICA and ruptured.6
CONCLUSIONS
In Allen et al. study, they recognized a subset of patients with CMAs who
are strongly immunocompromised and whose prognosis is dependent
on early recognition of their immune status and early
“invasive” treatment. They think that testing for immunocompromise
or atypical infections should be considered in a patient with
large or rapidly growing CMAs. Both endovascular and neurosurgical
techniques for treatment of CMAs are safe and effective. They
recommend more frequent angiographic follow-up and early invasive
repair, either endovascular or neurosurgical, as the new
standard of care for strongly immunocompromised patients presenting
with CMAs. Three conditions that Allen et al. have identified as
leading to strongly immunocompromised states are AIDS, chemotherapy,
and steroid immunosuppression. Endovascular repair
is preferred over neurosurgical repair in patients requiring
acute heart valve replacement from IE due to delays and
complications
with anticoagulation and prior reports of increased risk of
perioperative heart failure. They found lower overall mortality for
patients who received interventions (13% mortality) versus those
who received antibiotics alone (40% mortality). They found that
64% of CMAs treated with antibiotics alone completely regressed;
there was no apparent relationship between initial aneurysm size
and length of persistence on antibiotics, though their sample size
was small and the length of angiographic follow-up was variable.
Other limitations of Allen et al. study include its retrospective design,
the sequential rather than random selection of patients, and the
lack of standardized angiographic follow-up. Future studies may
include evaluation of the average duration of CMA persistence on
antibiotics with standardized angiographic follow-up and a
prospective
randomized trial comparing endovascular and neurosurgical
repair. Another limitation was the lack of adequate available
patient history and records for a truly definitive patient
classification
system into “strongly” or “relatively” immunocompromised
states. Future studies may examine other CMA patient risk factors
leading to strongly immunocompromised states so that these patients
may be stratified early for initial treatment purposes. Given
the rarity of CMAs, Allen et al. findings may further assist in treatment
planning for patients with known or suspected CMAs, particularly
in immunocompromised patients and in the acute period.
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1981;9:583–88MRI TWIST In brain dead patient. |
