Key-words: Aneurysmal subarachnoid - endovascular therapy - hemorrhage - neurogenic - pulmonary
edema - Takotsubo-like cardiomyopathy
Introduction
Outcomes of aneurysmal subarachnoid hemorrhage (aSAH) with Hunt and Hess (H and H)
Grades IV and V are still poor.[[1 ]] Such high-grade aSAH is likely to be complicated by cardiopulmonary dysfunction
such as neurogenic pulmonary edema (NPE) and Takotsubo-like cardiomyopathy (TCM).
NPE is estimated to be present in 2%–29% of patients with aSAH,[[2 ]] whereas TCM is thought to be present in 4%–15% of them.[[3 ]] It is important to diagnose aSAH-associated NPE and TCM because they are not only
critical conditions necessitating prompt and appropriate managements but also important
prognostic factors.[[4 ]],[[5 ]],[[6 ]] Endovascular therapy has become a popular alternative to open microsurgical clipping
in the treatment of aSAH.[[7 ]],[[8 ]] However, there are very few reports documenting the efficacy of endovascular therapy
for patients with aSAH complicated by NPE and TCM.[[8 ]] The present study aimed to validate it.
Materials and Methods
The present study was performed in accordance with the human ethical guidelines of
our institution. Written informed consent was obtained from all the patients upon
commencement of this study. Initially, medical records of the patients who were diagnosed
with aSAH and treated by endovascular therapy over the past 5 years were retrieved
from the Juntendo University Urayasu Hospital database. Among them, files of cases
complicated by NPE and TCM were extracted for analysis. For the period, we assessed
aSAH grade at presentation with H and H scale, and endovascular therapy was chosen
as the first-line measure for the treatment of patients with aSAH, regardless of the
sites responsible for cerebral aneurysms. Clinical criteria for NPE included auscultation
of crackles suggesting fluids in the lungs and bronchi, in addition to chest radiography
showing diffuse infiltrates within the lung fields.[[4 ]],[[5 ]] Clinical criteria for TCM included echocardiographic findings, indicating abnormal
motions in the regional walls. In addition, elevation and depression in ST-T segment,
prolongation of QT interval, and inversion of T-wave were recorded as supplementary,
abnormal electrocardiographic findings that could be associated with cardiac dysfunctions.
The cardiologists diagnosed as NPE and TCM. We chose endovascular therapy for all
the ruptured cerebral aneurysms complicated by NPE and TCM. During endovascular procedures,
heparin was intravenously administered so as to maintain activated clotting time approximately
at twice the normal control value. At the start of the procedure, a 6 Fr guiding sheath
was deployed in the parent vessel through the right femoral artery. A microcatheter
was advanced through the guiding catheter until the tip reached near the neck of aneurysm.
Then, the aneurysm was embolized with platinum coils. The NPE and TCM were not treated
during endovascular procedures, just starting to manage immediately after the procedure.
We stabilized general condition of the treated patients with cardiologists during
acute phase after endovascular therapy. Cardiologists checked the chest radiography,
echocardiography, gain or loss of daily total fluid balance, and electrocardiographic
findings of the patients. When a total fluid balance was assessed to be excessive,
more than 1500 ml/24 h, or the patients' respiratory status got worse with an emergence
of infiltrates on chest radiography, intravenous administration of diuretics (furosemide:
5–20 mg/day) was started. Furthermore, mechanical ventilation was conducted with sedatives
for altered conditions caused by NPE and TCM. A positive pressure ventilation was
performed set at 5–8 mmHg. If patients' systolic blood pressure decreased below 80
mmHg, continuous intravenous infusion of vasopressor was started for maintaining it
above 120 mmHg. Outcome of the treatment was evaluated, and grades were assigned to
individual patients on the Modified Rankin Scale (mRS) after 6 months of discharge.
Results
In total, thirty patients underwent microsurgical clipping for ruptured cerebral aneurysms,
and 74 patients underwent endovascular therapy between September 2013 and December
2018. Endovascular therapy group comprised 54 males and 20 females, with a mean age
of 59.5 ± 13.6 years (range: 28–89 years). In patients belonging to the group, SAH
grades at presentation that were assessed with H and H grade were as follows: Grade
I for 9 patients, Grade II for 20, Grade III for 14, Grade IV for 9, and Grade V for
19. In 74 patients, ruptured aneurysms were located in the anterior circulation, whereas
in 5, aneurysms were identified in the posterior circulation. Ten of the 104 patients
with ruptured cerebral aneurysms (9.6%) were complicated by NPE and TCM. Further,
abnormal electrocardiographic findings were identified in all the ten patients. These
results were variable, and there was no specific finding. The patients underwent coil
embolization within 72 h from the onset for obliterating ruptured aneurysms, following
careful evaluation of the cardiopulmonary function and stabilization of general condition.
All the ten patients were female, presenting with H and H Grade II (one patient),
Grade III (three patients), Grade IV (one patient), and Grade V (five patients) [[Table 1 ]]. Locations of ruptured aneurysms were as follows: the internal carotid artery–posterior
communicating artery (ICA-PCoA) junctional site in five patients, anterior communicating
artery in two, intracranial vertebral artery (VA) in two, and middle cerebral artery
in one. Two aneurysms identified on the VA were considered as dissecting in etiology
based on their clinical symptoms and angiographical appearance. Compared to the anterior
circulation, NPE and TCM were more frequent complications in patients with aneurysms
of the posterior circulation (11.6% vs. 40.0%). For seven patients, endovascular procedure
was carried out under general anesthesia, whereas three underwent the procedure with
local anesthetics and intravenous sedatives for low ejection fraction of <20%. These
aneurysms were successfully embolized without any identifiable endovascular procedure-associated
complications. In all the patients, time taken from the placement of guiding sheath
into the femoral artery to the completion of the coiling was within 2 h. The mRS score
at 6 months after discharge from the hospital was 0 in four patients, 1 in two, and
3 in one. Thus, the outcome of seven patients (70%) was favorable with a mRS score
of 0–3. In the remaining three patients, mRS was 5. In patients who underwent endovascular
therapy but were not present NPE or TCM, the mRS score at 6 months after discharge
was 0–3 in 48 patients, 4–5 in 11, and 5 in 6. The favorable outcome (mRS: 0–3) without
NPE and TCM was 75.0%.
Table 1: Summary of 10 cases complicated by neurogenic pulmonary oedema and takotsubo-like
cardiomyopathy
Illustrative case 1
A 54-year-old previously healthy woman with severe headache, disturbed consciousness,
and H and H Grade V was referred to our hospital. Her blood pressure at the time of
presentation was 88/50 mmHg, and the oxygen saturation was 82% without external administration
of pure oxygen. Her chest radiography revealed diffuse infiltrates, bilaterally in
the lung fields with crackles on auscultation [[Figure 1 ]]. Electrocardiography demonstrated abnormal depressions in ST-T segments. Cardiac
echocardiography showed abnormal motions in the left ventricular walls, consistent
with TCM. The ejection fraction was assessed to be 10%. Emergent catheter angiography
demonstrated that there were no coronary lesions responsible for cardiac dysfunction.
Noncontrast cranial computed tomography (CT) scans at the presentation showed diffuse
thick SAH and accompanying mild ventriculomegaly [[Figure 2 ]]. Three-dimensional CT angiography revealed a saccular aneurysm at the left ICA-PCoA
junctional site, measuring 11 mm in maximum dimension. Based on these findings, the
patient was diagnosed with aSAH complicated by NPE and TCM. The patient underwent
coil embolization with local anesthetics and intravenous administration of midazolam
for severely depressed cardiac function. The aneurysm was successfully embolized without
identifiable procedure-associated complications [[Figure 3 ]] and [[Figure 4 ]]. Echocardiographic findings of the patient showed a gradual improvement with resolution
of signs of pulmonary edema on chest radiography in the following 1 week. After placement
of a ventriculoperitoneal shunt for persistent communicating hydrocephalus, the patient
was discharged on the 56th day after the operation with mRS 2.
Figure 1: Chest X-ray, anteroposterior view, showing diffuse infiltrates bilaterally in the
lung field indicating pulmonary edema
Figure 2: Noncontrast axial computed tomography scans taken at presentation showing diffuse
subarachnoid hemorrhage and mild ventriculomegaly
Figure 3: Three-dimensional left internal carotid angiography, oblique view, showing a saccular
aneurysm (arrow) on the internal carotid-posterior communicating artery junctional
site. ICA: Internal carotid artery; PCoA: Posterior communicating artery
Figure 4: Left internal carotid angiography, after coil embolization, showing successful obliteration
of the aneurysm
Illustrative case 2
A 35-year-old previously healthy woman sustained abrupt disturbance of consciousness
2 days after delivery, during hospitalization in our hospital. She was discovered
to be comatose with H and H Grade V. Noncontrast cranial CT scans showed diffuse and
thick SAH [[Figure 5 ]]. Her chest radiography revealed diffuse infiltrates, bilaterally in the lung fields
with crackles on auscultation [[Figure 6 ]]. Electrocardiography demonstrated abnormal depressions in ST-T segments. Cardiac
echocardiography showed abnormal motions in the left ventricular walls, consistent
with TCM. The ejection fraction was assessed to be 10%. Three-dimensional CT angiography
revealed a fusiform dissecting aneurysm at the right VA, where the right posterior
inferior cerebellar artery (PICA) was found to arise from the dome of the aneurysm
[[Figure 7 ]]. Based on these, the patient was diagnosed with aSAH complicated by NPE and TCM.
The patient underwent coil embolization with local anesthetics and intravenous administration
of midazolam for severely depressed cardiac function. The aneurysm was successfully
occluded involving the original site of the right PICA and a segment of the VA proximal
to the site [[Figure 8 ]]. Territory of the right PICA was perfused by the left PICA and ipsilateral right
anterior inferior cerebellar artery, and there were no procedure-associated complications
after surgery. The patient was under control of mechanical ventilation for 2 weeks
because of the disturbed cardiac function. Her echocardiographic findings showed a
gradual improvement with resolution of signs of pulmonary edema on chest radiography
in the following same 2 weeks. After placement of a ventriculoperitoneal shunt for
persistent communicating hydrocephalus, the patient was discharged with mRS 0.
Figure 5: Noncontrast axial computed tomography scans taken at the onset showing diffuse subarachnoid
hemorrhage
Figure 6: Chest X-ray, anteroposterior view, showing diffuse infiltrates bilaterally in the
lung field indicating pulmonary edema
Figure 7: Three-dimensional right vertebral artery angiography, oblique view, showing a fusiform
aneurysm (arrow). The right posterior inferior cerebellar artery arises from the dome
of the aneurysm (arrowheads)
Figure 8: Right vertebral angiography, after coil embolization, showing successful obliteration
of the offending aneurysm involving the original site of the posterior inferior cerebellar
artery and a segment of the vertebral artery proximal to the site
Illustrative case 3
A 47-year-old previously healthy woman suddenly sustained severe headache and disturbed
consciousness, who was referred to our hospital in H and H Grade III. Cranial CT scans
showed diffuse SAH [[Figure 9 ]]. Three-dimensional CT angiography revealed a fusiform aneurysm on the left VA,
where the left PICA arose from the dome of the aneurysm. Her chest radiography revealed
mild infiltrates bilaterally in the lung fields with crackles on auscultation. Electrocardiography
demonstrated abnormal depressions in ST-T segments. Cardiac echocardiography showed
abnormal motions in the left ventricular walls, consistent with TCM. The ejection
fraction was assessed to be 30%. Therefore, we diagnosed that the patient was aSAH
complicated by mild NPE and TCM. The patient underwent coil embolization under general
anesthesia. On catheter angiography, the left PICA arose from the dome of the aneurysm
[[Figure 10 ]]. The aneurysm was successfully embolized with a segment of the left VA and the
original site of the PICA [[Figure 11 ]]. Postoperatively, procedure-associated complications were not noted. The patient
extubated the next day of embolization; however, her respiratory status gradually
deteriorated by progression of NPE and TCM. Then, the patient was again intubated
on postembolization day 6 and was treated of NPE and TCM with diuretics and continuous
intravenous administration of sedatives, under mechanical ventilation. Echocardiographic
findings of the patient showed a gradual improvement with resolution of signs of pulmonary
edema on chest radiography in the next 1 week. Her respiratory status was gradually
improved after 2 weeks. Although posttreatment cerebral magnetic resonance imaging
showed an ischemic region in the occluded PICA territory [[Figure 12 ]], the patient was discharged with mRS 1 on the 38th postoperative day without ventriculoperitoneal
shunt.
Figure 9: Noncontrast axial computed tomography scan taken at the presentation showing diffuse
subarachnoid hemorrhage
Figure 10: Three-dimensional left vertebral angiography, oblique view, showing a fusiform aneurysm
(arrow). The left posterior inferior cerebellar artery arises from the dome of the
aneurysm (arrowheads)
Figure 11: Left vertebral angiography after coil embolization, oblique view, showing successful
obliteration of the offending aneurysm involving the original site of the posterior
inferior cerebellar artery and a segment of the vertebral artery proximal to the site
Figure 12: Axial fluid-attenuated inversion recovery image after 6 months of discharge showing
ischemic changes in the territory of the left posterior inferior cerebellar artery
(encircled area)
Discussion
Despite extensive investigations, studies on the outcome of patients with high-grade
aSAH are still limited.[[1 ]] In the present study, 60% of the cases complicated by NPE and TCM had high-grade
aSAH. The most frequent location of the aneurysms was the ICA-PCoA junctional site,
although previous reports documented a predisposition for the posterior circulation.[[2 ]],[[3 ]],[[4 ]],[[5 ]],[[7 ]],[[8 ]],[[9 ]],[[10 ]],[[11 ]] The discrepancy may be attributed to the small population of the present study.
There were no complications associated with the endovascular procedures. Furthermore,
70% of outcomes were favorable as assessment after 6 months revealed a mRS score of
0–3.
NPE has been described as the consequence of various types of brain injury, head trauma,
seizure, and intracranial hemorrhages.[[12 ]] Kato et al. documented that clinical conditions associated with high catecholamine
levels caused by diverse pathologies, acute SAH accompanying sympathetic storm, and
acute thyrotoxicosis could cause TCM.[[12 ]]
There has been a marked difference in the incidence of SAH between both the sexes,
with females being the more frequently afflicted. Deshmukh et al. reported that women
are at nine times higher risk of developing TCM compared with men.[[13 ]] Furthermore, in aSAH cases complicated by NPE and TCM, there was a clear female
preponderance.[[10 ]] In the present study too, all the cases complicated by NPE and TCM were of female
patients. We are yet to identify the reason behind such an observation.
Yabumoto et al. have proposed an early surgical intervention for ruptured aneurysms
and management of NPE, claiming that NPE should not be an obstacle to radical intervention
when cardiorespiratory control can maintain the minimal anesthetic limit.[[11 ]] Neurosurgeons may encounter a dilemma when they treat aSAH complicated by NPE and
TCM.[[10 ]] To date, however, an optimal treatment strategy for such aSAH has not been defined.
Recent studies recommend early intervention with an endovascular procedure for aSAH
cases complicated by NPE and TCM.[[2 ]],[[8 ]],[[14 ]] Advantages of endovascular therapy for such patients involve less invasiveness
and a short duration for completing the procedures.[[7 ]] In any of our ten patients, time taken from the placement of the guiding sheath
to the completion of coiling was within 2 h.
An induced hypertension for aSAH patients with normal cardiopulmonary functions is
recommended to prevent delayed ischemic neurological deficit caused by cerebral vasospasm.[[15 ]] The therapeutic strategy is, however, contraindicated in cases complicated by NPE
and TCM. Cardiac prognosis related to TCM is commonly favorable for its self-limiting
nature with usual resolution in a few weeks.[[16 ]] However, once TCM has complicated with a high-grade aSAH, the treatment becomes
challenging with risks of cardiopulmonary arrest and death.[[17 ]],[[18 ]]
There are certain limitations in the current study. First, it was a retrospective
review of patients who were treated by coil embolization. Second, the treatment outcome
of the study was not compared with that provided by open microsurgical clipping. Furthermore,
as the study involved only ten patients, the obtained results cannot provide a definitive
conclusion. A well-designed, randomized study involving a sufficiently large population
is necessary to establish an appropriate therapeutic strategy for aSAH cases complicated
by NPE and TCM. Because of a retrospective analysis, our study did not compare two
populations with and without NPE and TCM who underwent endovascular treatment. Future
investigation should need the comparison.
Conclusions
Although treatment outcome of high-grade aSAH is still poor, we consider that endovascular
therapy can be a feasible alternative treatment for patients with high-grade aSAH
complicated by NPE and TCM.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
