Keywords
outcome - poor grade - subarachnoid hemorrhage - surgery - treatment
Introduction
Intracranial aneurysms are dilations of cerebral arteries caused by hemodynamic and
structural changes. Most aneurysms develop spontaneously, while only 1 to 2% are associated
with trauma, infection, or tumor.[1]
[2]
[3]
[4]
[5] In more than 80% of cases, the cause of subarachnoid hemorrhage (SAH) is rupture
of the intracranial aneurysm. Large autopsy series have shown that approximately 5%
of the population develops an aneurysm at some stage of life.[6] According to a large study series, the initial clinical status determines the outcome.[2] Of all patients with SAH, 3 to 18% of them die at the time of hospitalization as
well as 40% of those treated in hospital.[7]
Clinical and neurological status is most commonly determined using the Hunt and Hess
(HH) score. The most common causes of patient deterioration is re-hemorrhage or high
HH score. HH score as well as aneurysm diameter was directly related to early rehemorrhage.[8] There is a closed correlation of 75% HH score 5 patients and vasospasm, whereas
this is observed in only 2% of patients with an HH score of 1. It is known that mortality
is increased in patients with an HH score 5. The incidence of re-hemorrhage is the
highest within 24 hours of the hemorrhage, while mortality after re-hemorrhage is
up to 75%.[2]
[9]
[10]
[11]
[12]
[13]
Given the high mortality of patients with poor HH score and high rate of hemorrhage,
the aim of this study was to evaluate the clinical characteristics and outcome of
poor-grade aneurysmal SAH at our institution.
Patients and Methods
We performed a retrospective study that included all patients who were treated in
the Department of Neurosurgery, Clinical Center University of Sarajevo, with a diagnosis
of aneurismal subarachnoid hemorrhage from January 1, 2015, to December 31, 2020.
This study was approved by our institution ethics committee. Informed concent was
taken from legal guardians of patients. All aneurysmal SAH (aSAH) were diagnostic
with the CT and CT angiography of the brain or DSA. Demographic and clinical data
were collected from the patient's history. The HH scale was used to assess the severity
of aSAH, while Fisher's scale was used to measure the amount of blood appearing on
the computed tomography (CT). Both scales were documented on admission to the hospital.
Inclusion criteria were patients with an HH score 4 or 5, patients older than 18 years,
and patients with complete medical documentation.
The term “poor-grade SAH” refers to patients who were classified as score 4 or 5 according
to the HH score at the time of admission to the hospital.[14]
Based on the admission, Glasgow Coma Score (GCS) patients were divided into three
groups: GCS (8–12), GCS (5–8), and deepest coma GCS 3 and 4. The location of the aneurysms
was divided into nine groups according to the occurrence in the projection of the
Willis circle.
As a treatment modality, interventional treatment was performed in the form of microsurgery
or endovascular treatment, depending on the interdisciplinary approach to each patient.
All patients with acute hydrocephalus or intraventricular hemorrhage were treated
with external ventricular drainage. When patients present with bilateral dilated pupils,
impaired blood flow on transcranial Doppler (TCD), massive hematoma in the basal ganglia
of the dominant hemisphere or hematoma in the brainstem occur, they are treated conservatively.
We defined the final outcome in the form of a modified Rankin score (mRs) at the discharge.
Excellent and satisfactory outcome imply positive outcome mRs 0 to 4.
Statistical analysis was performed with GraphPad software. Continuous variables were
presented as mean ± standard deviation (SD), and categorical variables as frequency
(percentage). Categorical variables were analyzed using the Fisher exact test and
the unpaired t-test for parametric values. p-Values less than 0.05 were considered statistically significant.
Results
During the study period, 5,615 patients were admitted to our hospital, 415 of whom
had a cerebral aneurysm. Poor-grade SAH patients represent 2.35% of the general neurosurgical
patients and 31.08% (n = 132) of the total number of aneurysms. The youngest patient aged 26 years and the
oldest aged 86 years, with an average age of 57.7 years ([Table 1]).
Table 1
Baseline clinical characteristics of patients
|
Characteristic
|
n = 132
|
|
Gender
|
|
Male
|
44
|
|
Female
|
88
|
|
Age (y)
|
57.7 ± 12.25
|
|
GCS at admission
|
|
GCS 8-12
|
4
|
|
GCS 5-8
|
26
|
|
GCS 3-4
|
76
|
|
Hunt and Hess
|
|
Grade IV
|
25
|
|
Grade V
|
107
|
|
Fisher grade
|
|
Grade I
|
2
|
|
Grade II
|
2
|
|
Grade III
|
21
|
|
Grade IV
|
107
|
|
Location of aneurysm
|
|
anterior circulation
|
113
|
|
posterior circulation
|
19
|
|
Treatment modality
|
|
endovascular
|
4
|
|
Microsurgical
|
67
|
The most common age group was group 51 to 69 years, which was 57.6%, followed by groups
over 70 years and 31 to 50 years, with 24% of patients each. In our cohort, we had
25 patients with an HH score 4 (18.9%), whereas there were 107 patients with an HH
score 5 (81.1%). The majority of patients (81.1%) were in Fisher grade 4.
Most patients in this study were in a deep coma ([Table 1]). According to the aneurysm location, the most common aneurysmal location was middle
cerebral artery in (in 33%), followed by anterior communicating artery (in 28%) and
internal carotid artery (in 16%) ([Fig. 1]).
Fig. 1 Location of the source of bleeding in “poor-grade patients”. MCA dominance was found
in more than 33% of cases, followed by AcoA aneurysms and ICA complex aneurysms. In
case of multiple aneurysms, no significant source of bleeding could be identified
with certainty. MCA, middle cerebral artery; Pcom, posterior communiacting artery;
ICA, internal carotid artery; AcoA, anterior communicating artery; M, multiple aneurysms;
VA, vertebral artery; PICA, posterior inferior cerebellar artery; iSAH, idiopathic
SAH; DACA, distal anterior cerebral artery; BA, basilar artery.
There is also predominance of aneurysm of the anterior location (85.6% of patients).
Of all patients, 71 patients were treated surgically or underwent endovascular treatment
([Table 1]). We had 61 (46.2%) conservatively treated patients due to their clinical state.
For interventional, primarily surgically treated patients, a positive outcome (mRs
0–4) was found in 49.25% of patients with a mortality of 42.3%. However, excellent
outcome (mRs 0–2), was found in 30.38% of surgically treated patients and 19.36% of
general poor-grade SAH patients.
Analysis of Treatment
Our study showed that patients aged 51 to 69 years were the most frequently treated;
however, there were statistically significant differences in the representation of
patients in certain age groups by type of treatment. Patients who were treated conservatively
were most often in the older age group of over 70 years (p = 0.002). Patients undergoing endovascular treatment were in the age group 31 to
50 years (75.0%), whereas surgically treated patients were mostly in the age group
51 to 69 years (64.2%). In addition, conservatively treated patients were the oldest
with a mean age of 62.97 ± 12.31 years, while surgically treated patients had a mean
age of 55.64 ± 12.13 years. Statistical analysis using the Mann–Whitney U test for independent samples showed that there was a statistically significant difference
in the mean age between treatment types (p = 0.006), as well as a negative correlation with higher age group (p = 0.028–0.003). There was a statistically significant difference between the choice
of treatment type with respect to the patient's age. It should be noted that most
elderly patients are in a deep coma.
According to the state of consciousness, conservatively treated patients were more
often in coma 54 (88.5%) compared to surgically treated patients 53 or 74.6% (p = 0.042). Comparison of the degree of coma depth according to the GCS scale and the
type of treatment showed a statistically significant difference between the type of
treatment and the degree of coma depth (p = 0.0001). Also, 80.3% (n = 49) of conservatively treated patients were in deep coma compared to 46.5% (n = 33) treated with final aneurysm intervention ([Fig. 2]). Analysis of treatment modality versus aneurysm location revealed no statistically
significant difference in final outcome.
Fig. 2 The relation of the state of consciousness measured by GCS score with a choice of
type and group of treatments. A comparison of the degree of coma depth according to
the GCS scale and the types and groups of treatment shows that there is a statistically
significant difference between the types of treatment according to the depth of coma
(p = 0.0001).
As expected, we found the lethal outcome of conservatively treated patients in 94.9%
(n = 37/39) as well as in those treated with external ventricular drainage without final
intervention on the aneurysm (100%). For surgically treated patients, we found a positive
outcome in 34.3% (n = 23) with lethality in 43.3% of patients (n = 29). For the same group of patients, we had a satisfactory outcome in 14.9% (n = 10) patients, while a poor outcome was recorded in 7.5% (n = 5) patients. Statistical analysis indicates a highly significant difference between
treatment types and treatment outcomes.
Outcome of Surgically Treated Patients in Relation to the HH Score
Surgical treatment was mostly performed in HH score 5 patients compared with the HH
score 4 group. In general, we found a positive outcome in 47.1% (n = 8) of the HH score 4 compared with 30.0% (n = 15) of the HH score 5 group. Satisfactory and poor outcomes were found in 11.8%
of HH score 4 (n = 2) with lethal outcome in 29.4% (n = 5) of patients. In HH score
5, we found a satisfactory outcome in 16.0% (n = 8/50) patients, while a poor outcome was seen in 6.0% (n = 3) patients, with 48% (n = 24) have a lethal outcome. There was no statistically significant difference or
correlation between HH score and treatment outcome (p > 0.05). Although there is a better outcome in HH score 4 patients; both groups have
a significant benefit from surgical treatment. The regression model shows that treatment
and location have a statistically significant predictive potential for lethal outcome,
while age, HH score, GCS, and Fisher grade have no predictive potential (odds ratio
[OR] = 2.070 and p = 0.001) ([Table 2]).
Table 2
Predictive factors of mortality in regression model
|
Predictor
|
β
|
SE
|
Wald
|
df
|
Significant
|
Odds ratio
|
Lower
|
Upper
|
|
Age
|
0.032
|
0.020
|
2.493
|
1
|
0.114
|
1.033
|
0.992
|
1.075
|
|
Hunt and Hess score
|
1.456
|
1.064
|
1.871
|
1
|
0.171
|
4.287
|
0.532
|
34.518
|
|
Glasgow Coma Score
|
−0.078
|
0.564
|
0.019
|
1
|
0.890
|
0.925
|
0.306
|
2.796
|
|
Fisher grade
|
0.488
|
0.452
|
1.166
|
1
|
0.280
|
1.628
|
0.672
|
3.946
|
|
Treatment
|
−2.198
|
0.537
|
16.767
|
1
|
0.000
|
0.111
|
0.039
|
0.318
|
|
Location
|
−0.225
|
0.110
|
4.215
|
1
|
0.040
|
0.798
|
0.644
|
0.990
|
|
Constant
|
−3.266
|
4.733
|
0.476
|
1
|
0.490
|
0.038
|
|
|
Abbreviations: β, beta coefficient; df, degrees of freedom; SE, standard error.
Discussion
In this study, we evaluated the clinical characteristics and outcome of poor-grade
aneurysmal SAH at our institution. We have found that primarily, surgically treated
patients with HH score 4 or 5 have a positive outcome (mRs 0–4) in 49.25% of patients,
with a mortality of 42.3%.
The final outcome of treatment of “poor-grade SAH patients” is difficult to predict.
Poor clinical grade is also possible as a consequence of intracerebral hematoma, increased
intracranial pressure, hydrocephalus, and due to herniation of brain structures.[15] We have found in this study that patients with poor-grade SAH have a positive outcome
in terms of mRs (0–4) in 49.25% of the patients who underwent interventional treatment.
Comparing isolated mortality, it was clearly defined as 83% in the earlier era versus
39% in the current era with a slightly higher mortality of our patients of 43.28%,
but without the option of endovascular treatment at full capacity. A recent study
from 2020 goes a step further in assessing the early aggressive treatment of patients
with HH score 5, and those in the deepest degree of coma (GCS 3–5). Although the mortality
rate is 65.8%, those who survive are able to live alone or with the help of another
person in 85.5% of cases.[10] Our mortality results of the total sample correlate with the above study and are
67%. From a comparative point of view, the best chance of a favorable outcome is exclusively
for patients who have been treated surgically, when we decide that the treatment is
justified. Thus, some studies show a survival in 38% of patients 1 year after SAH
and 73% in the period of 3 months after bleeding.[16]
[17] In our study, we recorded similar results for conservatively treated patients, who
usually die at early intrahospital stage. We determined similar criteria for the selection
of patients to be treated conservatively, with GCS scale that is usually 3 or 4 for
such patients.
Moreover, we believe that aneurysms, especially localizations on the MCA, should be
urgently treated with the accompanying evacuation of the intracerebral hematoma. If
edema is expected or recorded, our surgical strategy is projected toward approach,
incision planning, and larger, sometimes decompressive craniotomy. It is important
to emphasize that a worse outcome was recorded in patients with presented intracerebral
hematoma, whether evacuation of the hematoma was performed or not. However, the choice
of decompressive craniectomy shows no long-term benefit.[18]
Ellenbogen[15] showed that early aggressive treatment involving EVD, and ultra-early aneurysm intervention
results with mortality of 50%. Our results suggest a slightly lower mortality of 43.28%
compared with the previous study, and predominantly surgical treatment was performed.
In the same study, 26 surviving patients underwent neurophysiological examination,
and an excellent outcome was noted in terms of cognitive brain function in surgical
versus endovascular treatment.[15] A study conducted on 248 patients with “poor-grade” SAH showed a 24% favorable outcome
mostly in WFNS 4 (61%). In our study, most patients were HH score 5, which would correspond
to the WFNS score 5. Some authors reported a favorable outcome in 36% of treated and
24% of the total number of patients with WFNS grade 5 in the case of early intervention
within 24 hours.[19] Compared with our study, we recorded a statistically significant positive deviation
of our results in terms of outcomes in general but also relative to the HH group.
The possible bias of the results can be observed in the determination of determining
a positive outcome.
A study from India on 2,039 patients shows an increase in favorable treatment outcome
to 30% in patients with “poor-grade” SAH patients measured with the GOS with a male/female
ratio of 51:49%. Interventional treatment for “poor grade” patients is performed only
if patients show neurological recovery.[20] In another study, 30% of patients with HH score 4 had a good outcome after surgical
occlusion, as opposed to 11% of patients with HH score 5.[15] Zeng et al showed a significant reduction in mortality in surgical versus conservatively
treated patients in early-treated patients, within 24 hours. The results of this study
are better compared to our positive outcome of our results of 44.17% for HH 4 patients,
but significantly worse compared to the 19% of favorable outcome for HH score 5 patients
of our study. The Barrow Neurological Institute study from 2018 shows mRs 2 outcome
observed in 55% of poor-grade patients on ACM aneurysms.[21]
[22]
Depending on the studies and data sources, we can conclude that a favorable outcome
can usually be achieved in the range of 30 to 65% of patients. Our results of surgical
treatment are close to the average results of recent studies. Still, a positive outcome
in terms of mRs (0–4) was observed in 49.25% of the patients who underwent interventional
treatment.
Recent studies analyze the influence of location on the outcome of patient outcome.
Thus, a 10-year study from the United States with 2,152 aneurysms confirmed that anterior
communicating artery (ACoA) complex aneurysms were the dominant location. Similar
data were reported in other studies.[22]
[23] Another German study showed an increase in the percentage of ACM (27% ACM) aneurysms
and a significant decrease in the number of ICA aneurysms.[24] Our data reported 33.3% of patients with ACM aneurysms. As a possible cause for
the more frequent occurrence of ACM location, in our study, the presence of intracerebral
hematoma is very common, which brings the patient to the neurosurgeon earlier. A similar
pattern of occurrence was observed in the total number regardless of HH score, in
23.5% of the total 415 aneurysms in the 5-year period. Also, the increase in the percentage
of early interventional treatment of incidental on the reduction in the number of
ruptured aneurysms in the internal cerebral artery (ICA) is possible.
Male gender and younger age are associated with favorable outcome after poor-grade
SAH.[9] Of all patients, 66.4% were female, which in consistence with others studies.[13] Although the percentage of complications and poor outcomes is related to age, the
current view is that patients in the geriatric population, including those over 80
years, should be treated surgically, if the quality of life was satisfactory before
SAH. Patients up to the age of 60 years of age should definitely be treated.[15] Analyzing the mortality of the elderly population, one study argues in favor of
a statistically significantly worse outcome in patients with SAH who are older than
65 years. Nevertheless, a favorable outcome was observed in 31% of treated patients
with a dominant PCom localization, and most patient underwent endovascular treatment.[25] When comparing our results, we found that mortality as well as the outcomes did
not correlate in the negative sense of our results. ACM aneurysms where dominate in
our population. Another study from India in the geriatric population with “poor-grade”
SAH showed a favorable outcome in terms of GOS in 48% of treated patients if treatment
is delayed for 9 to 14 days after bleeding.[26] In our study, the geriatric population accounted for one-fifth of the patients.
Our study showed that in the elder population, the outcome is significantly worse
after 60 years. Our results have shown that mortality is more common in the geriatric
population.
Some recent studies suggest delaying treatment of patients with “poor-grade” until
the patients recover on the HH scale with a favorable outcome. Early surgery and aggressive
medical treatment resulted in better outcomes in 7 to 42.6% of patients.[27]
[28]
[29] Although some studies emphasize the treatment of aneurysms as an emergency within
72 hours of bleeding,[21]
[30] but the ideal timing of the intervention is still not clear. Konczalla et al[24] suggest significant survival and favorable outcome for comatose patients defined
as mRs 0 to 3 for comatose patients if early and aggressive treatment is initiated.
Potential positive outcome factors include younger age, normal pupillary response,
development of early hydrocephalus, and positive bilateral corneal reflex. Delaying
the treatment of patients with score HH 4 and 5 is no longer justified and that early
aggressive treatment, whether endovascular or surgical, is necessary.[24]
Limitations
The study has several limitations. The study was designed as a retrospective study
with subsequent insight into patient histories through the medical records with available
data without socio-epidemiological and etiological link. Also, there is no adequate
ratio of surgical versus endovascularly treated patients and it is not possible to
make comparative results regarding “poor-grade SAH” patients.
Conclusion
In our study, a comprehensive analysis of 132 “poor-grade aneurysmal SAH” patients,
most patients presented as HH score 5, and GCS 3 and 4 was performed. For interventional,
primarily surgically, treated patients, a positive outcome (mRs 0–4) was found in
49.25% of patients with a mortality of 42.3% in our study. Although there is a better
outcome in patients with HH score 4 compared to score 5, both groups have a benefit
from surgical treatment. However, excellent outcome (mRs 0–2) was found in 30.38%
of surgically treated patients or 19.36% of general poor grade SAH patients. This
study has shown that patients with HH score 4 and 5 should not be surgically abandoned,
they need an active treatment to get the best possible results. However, we believe
that our study can represent a solid basis for further research.
