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11(05), 409-419
Article DOI:10.21474/IJAR01/16894
DOI URL: http://dx.doi.org/10.21474/IJAR01/16894
RESEARCH ARTICLE
CLINICO-DEMOGRAPHIC PROFILE AND CLINICAL OUTCOME OF YOUNG ADULT PATIENTS
WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE ADMITTED IN QUIRINO MEMORIAL
MEDICAL CENTER
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Corresponding Author:- Lester de Pedro Dimzon MD
ISSN: 2320-5407 Int. J. Adv. Res. 11(05), 409-419
In the Philippines, no local epidemiologic data has been published on young adults. However, a very alarming
increase in the number of hospital admissions of patients with ruptured aneurysm in the young adult population was
noted specifically in Quirino Memorial Medical Center (QMMC). Thus, this study will be conducted to determine
the incidence, the clinico-demographic profile and the clinical outcome of this specific population admitted at
QMMC.
Objectives:-
General Objective
To determine the clinico-demographic profile and clinical outcome of young adults with aneurysmal subarachnoid
hemorrhage admitted at Quirino Memorial Medical Center.
Specific Objectives
To determine the demographic profile of patients with ruptured aSAH as to:
1. age
2. sex
Clinicians. This study may help physicians in developing guidelines for secondary prevention or risk stratification of
patients with aSAH in this particular age group.
Government Institutions. The findings of this study may guide health policy maker in crafting policies directed
towards the provision of improved health care services specifically in the prevention and early diagnostics or
screening of patients who are at risk.
Researchers. The results of this study may be used as baseline information or support to researches on topics similar
or related to what is currently undertaken.
Conceptual Framework
Independent Variables Dependent Variable
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Figure 1. presents the interplay of variables within the study, where the role of independent variables (demographic
profile and clinical profile) affect the outcome of the study as per the number of survivors and non-survivors.
Aneurysmal SAH is relatively uncommon in patients younger than 40 years of age with rate of occurrence reported
as 10–20%. It is more common in women and in patients 40-60 years old. [7]. The male dominance among patients
with SAH has been observed in childhood and adolescence [3].
Studies have been conducted on a wide variety of possible risk factors for SAH; however, only a select few have
produced conclusive results [9]. Behaviors such as hypertension, smoking, excessive alcohol consumption, and the
use of sympathomimetic substances (such as cocaine) are all considered to be risk factors for aSAH [4]. Non-
modifiable risk factors for SAH include a family history of SAH in a first-degree relative, female sex, low educa-
tional achievement, low body mass index, and undetermined genetic factors.Some known inherited conditions asso-
ciated with SAH and/or intracranial aneurysms include adult dominant polycystic kidney disease (ADPKD), Ehlers–
Danlos disease (type IV), alpha1-antitrypsin deficiency, sickle cell disease, pseudoxanthoma elasticum, hereditary
hemorrhagic telangiectasia, neurofibromatosis type I, tuberous sclerosis, fibromuscular dysplasia, and coarctation of
the aorta [9].
Aneurysmal pathophysiology has been theorized to involve congenital weakness in the vessel wall, or degenerative
changes resulting in destruction of elasticity of the vessel wall at points of high turbulence such as bifurcations [7].
The pathophysiology that is associated with an aneurysm bursting is still being investigated, in the meantime. The
size and location of the unruptured aneurysm, as well as a previous history of SAH, are some clinical variables that
may be helpful in determining the risk of rupture of an unruptured aneurysm. Several investigators have evaluated
the histology and anatomic features of the aneurysm which may increase the risk of rupture [9].
Eighty-five percent of instances of aneurysmal SAH are caused by saccular (berry) aneurysms. Aneurysms that are
fusiform or mycotic occur less frequently. Intracranial aneurysms are usually solitary (70% to 75%) but may be
multiple in some patients (25% to 50%). The most common distribution for intracranial aneurysms includes the
following arteries: anterior communicating (30%), posterior communicating (25%), middle cerebral (20%), internal
carotid bifurcation (7.5%), and top of the basilar artery (7%) [9].
The complaint "the worst headache of my life" is the hallmark of aSAH in an awake patient, and it is mentioned by
80% of patients who can provide a history. In addition, 10% to 43% of patients also say that they have a warning or
sentinel headache before developing the aSAH-associated ictus. [4]. Symptoms that increase the likelihood of a
subarachnoid bleed as the cause of headache include exertional onset, syncope, vomiting, neck pain, and seizures.
Focal neurologic deficits, meningismus, and/or retinal hemorrhage may be present, but up to 50% of SAH patients
have a normal neurologic exam [7].
A non-contrast head CT is still the primary diagnostic tool for aSAH [4]. Sensitivity is nearly 100% for the first
three days, then gradually declines over the following few days as the subarachnoid blood clears due to spontaneous
lysis. [11]. If non-contrast head CT is not definitive, the next recommended diagnostic tool is the LP [7]. Lumbar
puncture is often required to show xanthochromia [4]. Magnetic resonance imaging (MRI) is not indicated as an
initial diagnostic test for SAH; however, it may be useful if the head CT findings are negative [9]. The challenge
with using MRI for SAH is that the blood is combined with CSF that has a high oxygen concentration, thus delaying
the transition of blood products to a deoxyhemoglobin state that is better imaged with MRI [7].
The most accurate way to diagnose intracranial aneurysms is still cerebral angiography. A “four-vessel” evaluation
of the bilateral internal carotid arteries and vertebral arteries is necessary [9]. CT angiography (CTA) on the other
hand, is emerging as an alternative diagnostic test for SAH; however, the diagnostic accuracy may be less than that
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of standard angiography [9]. Most experts concur that 2- and 3-dimensional cerebral angiography should be
performed after negative CTA in instances of diffuse aSAH pattern [4].
There are several systems of classification for SAH. The Hunt and Hess score and World Federation of Neurological
Surgeons grading system are both used to predict patient outcome, and the Fisher grade helps to predict vasospasm
[7]. One of the most popular grading systems in SAH, the Hunt and Hess scale, is built on a five-point scale, with
grade 5 being the most severe. Hunt and Hess grades 1-3 have a good prognosis and typically call for aggressive
therapy, whereas grades 4-5 have a mortality rate of 60–100%, making surgery less advantageous. Another five-
grade scale that is frequently used in clinical practice is the World Federation of Neurological Surgeons scale, which
has taken the position of the Hunt and Hess scale at many institutions. The prognosis is worsened by other variables,
such as advanced age, a pre-existing illness, hyperglycemia, sepsis, fever, delayed cerebral ischemia (DCI), and
rebleeding [11].
Initial management of the patient with SAH begins with the stabilization of the airway, breathing, and circulation.
Then attention turns to the institution of general supportive and neuroprotective measures, in anticipation of the
known complications of SAH [9]. Within 3 hours and almost half within 6 hours of the start of symptoms,
rebleeding occurs, and early rebleeding is linked to worse outcomes than later rebleeding [11]. To lower the rate of
rebleeding after aSAH, surgical clipping or endovascular coiling of the burst aneurysm should be carried out as soon
as is feasible in the majority of patients [4]. Coiling is the preferred method,since it is less invasive than open
surgical clipping, but guidelines suggest that coiling should be performed if both are possible [7]. Once the
aneurysm is secured, the greatest risk to patient outcome is that of vasospasm and delayed cerebral infarction (DCI)
[7].
One of the most frequent causes of death and disability in SAH is DCI, which includes vasospasm of the large
arteries. DCI most frequently occurs 7–10 days after aneurysm rupture and resolves on its own after 21 days. Oral
Nimodipine 60 mg given every 4 hours after 21 days of SAH demonstrated a significant decrease in both the
incidence of cerebral infarction and poor neurological outcomes at 3-months post-SAH in the British Aneurysm
Nimodipine Trial, which is the biggest research on this medication [11]. Upon the discovery of DCI, Triple-H
treatment may be started. There is currently no agreement on how Triple-H or each of its individual components
should be used, but it aims to improve cerebral perfusion in SAH patients with DCI. Triple-H therapy consists of
hypervolemia, hemodilution, and hypertension. Although prophylactic triple-H therapy for preventing DCI was
acceptable, current evidence does not support its efficacy and recommends maintaining normovolemia [5].
Follow-up imaging after endovascular aneurysm therapy is needed to determine the degree of aneurysm obliteration
in the treated aneurysm and assess for change in number and size of untreated aneurysms [10].
Research Methodology:-
Study Design
The study utilized the ambidirectional cohort study, since this research design is particularly significant for
analyzing exposures that may have both short and long-term outcomes, or even with more than one outcome. The
analysis of medical emergencies such as outbreaks, epidemics, or any other events that imply an unforeseen
exposure and for which data must be collected retrospectively can benefit from this kind of study [27].
Study Population
Inclusion Criteria
All Service and Pay patients aged 19-55 years old admitted from January 1, 2019 – December 31, 2020with
radiologically diagnosed ruptured aneurysmal subarachnoid hemorrhage using non-contrast Ct scan (NCCT), CT
angiogram (CTA), Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography (MRA), or Digital
Subtraction Angiography (DSA) irrespective of clinical presentation were included in the study.
Exclusion Criteria
1. Patients with aSAH aged less than 19 years old and more than 55 years old
2. Patients who were discharged against medical advice (DAMA) or transferred to other institution during the
study
The patients were selected as per protocol based on the inclusion and exclusion criteria.
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Setting/Location
The study was conducted at Quirino Memorial Medical Center, Quezon City, a tertiary hospital under the Philippine
Department of Health.
Sample Size
Convenience sampling was used in the study. The patients were selected as per protocol based on the inclusion and
exclusion criteria.
Study Variables
In this study, the clinical outcome of patients with ruptured aSAH was classified into two:
1. Survivor – This is defined as a patient who has ruptured aSAH and was discharged alive. The Modified Rankin
Scale will be utilized for scoring.(see Table 4 under Appendices.)
2. Non-survivor – These are patients who have ruptured aSAH and died as a direct cause of the disease.
Definition Of Terms
Stroke in the young - In the scientific literature on young adult stroke, the upper age cut-offs have varied from 30 to
65 years, being most commonly 50 or 55 in the recent literature. Although most of the scientific data come from
studies using a lower age cut-off [22]. In this study, “young adults” refer to aSAH occurring in adult people aged
less than 55 years.
Cerebral Aneurysm –This is a bulging, weakened area in the wall of an artery in the brain, resulting in an abnormal
widening, ballooning, or bleb [12].
aSAH – This refers to the extravasation of blood into the subarachnoid space caused by a ruptured aneurysm [13].
Hunt and Hess score – A scoring system used as a predictor of prognosis/outcome with a higher-grade correlating to
a lower survival rate [14], (Table 3 underAppendices)
Modified Fisher Grade score –A scoring system which classifies appearance of subarachnoid hemorrhage on head
CT scan [15].It is used in predicting cerebral vasospasm [25].
All data gathered were tabulated and reviewed by the researcher and a statistician. The data sheets were kept
confidential by the researcher until all data have been interpreted, after which they will be shredded after a year. No
other person has access to the documents, laboratories and other files of the study other than the researchers,
statistician and reviewers involved.
Descriptive statistics includes frequency and percentage to present clinical and demographic variables of the
respondents. Frequencies, percentages and means were used particularly in the tabular presentation of clinical and
demographic profile of the patients.
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For inferential analysis, a Fisher’s exact probability test was used to test for the analysis of two categorical variables
(either nominal or ordinal) for small sample sizes. The null hypothesis ofthe test will be rejected if the computed
exact p-value is less than the level of significance.The level of significance was set at 95% confidence interval [23].
Ethical Considerations
The identity of the patients included in this study were kept confidential and only coded numbers instead of names
were used to assure anonymity of the source. All data were encoded in a secure laptop with password and only the
researcher and statistician have access to them. The data gathered was saved during the entire duration of data
processing, writing of final paper until the final presentation of research. Once the final research output has been
presented and approved by the research committee, all records and raw data will be destroyed after a year. The data
contained in the laptop will be deleted and all notes pertaining to the study will likewise be discarded by shredding.
Significant data and results of this study may be presented to the medical community, and may be used as baseline
for future researches, and may be also cited as reference for other related studies. The anonymity of participants will
be kept with utmost confidentiality when research is shared during presentation in scientific forum or when
submitted for publication. In all instances, strict confidentiality will be maintained, and no information that will
identify the patient as participant will be disclosed.
An informed consent is no longer required from the participants as the data gathered are all part of the routine
interview and examination of the patients on initial consult and succeeding follow-up.
Based on the table, about 7 patients were19 to 35 years old and the remaining 24 patients are between 36 to 55 years
of age. Out of the 7 in the age bracket of 19 to 35 years old, 6 of them (85.7%) were safely discharged from the
hospital. On the other hand, only around 45.8% of the 36-55 years old age group were discharged from the hospital.
This is about half of the survival rate of the younger age bracket group. This may indicate that age is associated with
deaths due to aSAH. In particular, older patients have a higher risk of death from aSAH than younger patients.
However, based on the results of the Fisher’s exact test, a p-value of 0.073is insufficient to conclude that age is
associated with the mortality of patients with aSAH.
There are more men than women among SAH patientsboth in adolescence and in childhood. However, the reports
on the sex dominance in young adults are variable [3]. In the present study, male dominance was also noted. Of the
total of 31 patients, 19 (61%) were males and 12 (39%) were females, resulting in a male to female ratio of 1.6:1.
About two-thirds of the male patients were safely discharged from the hospital. On the other hand, two-thirds of the
female patients have died due to aSAH. This could be an indication that sex is related to aSAH-related mortalities.
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However, with a p-value of 0.061 on Fisher’s exact test there is insufficient evidence to claim that sex is associated
with the deaths of patients with aSAH. This is in contrast to the study done by S. Chotai et. al (2013). wherein they
observed that in the exact regression model, male sex predicted poor outcomes; however, they also added that this
difference reflects that intracranial aneurysm formation and growth may be linked to various factors in young adults
[3].
Table 2:- Clinical Profile of Young Adults with Aneurysmal Subarachnoid Hemorrhage.
Clinical Profile Outcome Total p-value b
Discharged Expired
Count %a Count %a Count %
Chief Complaint 0.0503
Loss of consciousness 1 16.7% 5 83.3% 6 19.4%
Others 16 64.0% 9 36.0% 25 80.7%
Smoking 0.725
Current smoker 9 64.3% 5 35.7% 14 45.2%
Non-smoker 7 46.7% 8 53.3% 15 48.4%
Quit smoker 1 50.0% 1 50.0% 2 6.5%
Comorbidity 0.727
Diabetes mellitus 1 50.0% 1 50.0% 2 6.5%
Hypertension 6 46.2% 7 53.8% 13 41.9%
None 10 62.5% 6 37.5% 16 51.6%
Family history of aSAH NA
No history 17 54.8% 14 45.2% 31 100.0%
Hunt and Hess Score 0.019*
1 8 66.7% 4 33.3% 12 38.7%
2 5 83.3% 1 16.7% 6 19.4%
3 4 66.7% 2 33.3% 6 19.4%
4 0 0.0% 4 100.0% 4 12.9%
5 0 0.0% 3 100.0% 3 9.7%
Modified Fisher Grade 0.113
Score
0 6 100.0% 0 0.0% 6 27.3%
1 2 50.0% 2 50.0% 4 18.2%
2 2 40.0% 3 60.0% 5 22.7%
3 3 42.9% 4 57.1% 7 31.8%
4 6 100.0% 0 0.0% 6 27.3%
Location of aneurysm 0.704
ACA 2 100.0% 0 0.0% 2 7.4%
ICA 2 66.7.0% 1 33.3% 3 11.1%
MCA 3 50.0% 3 50.0% 6 22.2%
PCA 1 100.0% 0 0.0% 1 3.7%
Acomm 5 41.7% 7 58.3% 12 44.4%
Pcomm 0 0.0% 1 100.0% 1 3.7%
BA 1 100.0% 0 0.0% 1 3.7%
VA 1 100.0% 0 0.0% 1 3.7%
Type of aneurysm 1.0
Berry 1 100.0% 0 0.0% 1 5.9%
Fusiform 1 100.0% 0 0.0% 1 5.9%
Saccular 9 60.0% 6 40.0% 15 88.2%
Number of aneurysms 0.569
Single 11 68.8% 5 31.3% 16 88.9%
Multiple 1 50.0% 1 50.0% 2 11.1%
a
Presents row percentages
b
p-values obtained from the Fisher’s exact test
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Table 2 presents the clinical profiles of the patients with aSAH. According to the majority of the literature, 80% of
SAH patients experience "the worst headache of my life," making it one of the most recognizable clinical
presentations in medicine.[11].Meanwhile, 50% of patients experience syncope, a condition that could be caused by
a sudden increase in intracranial pressure (ICP), which is greater than the mean artery pressure (MAP), leading to
critically low cerebral perfusion pressure (CPP) and widespread cerebral ischemia [9].Based on the table, about
19.4% of the patients have experienced a loss of consciousness or syncope. Other chief complaints from the patients
include headache (61.3%), a decrease in sensorium (9.7%), focal weakness and nape pain. Out of the 6 patients who
experienced a loss of consciousness, 5 of them died eventually. This may show that this initial presentation is
associated with the mortality of the patients. But based on the results of the Fisher’s exact test, the relationship is
deemed insignificant at a 5% significance level (p-value = 0.0503).
Young adults' aneurysm formation and rupture mechanisms are still poorly understood. One of the most crucial
elements in the development and expansion of aneurysms continues to be hemodynamic stress compounded by
hypertension. Atherosclerosis is the main cause of the internal elastic lamina's degeneration, which appears to be
necessary for aneurysm formation. [3]. An aneurysmal cause of SAH has similar risk factors associated with
aneurysm formation. The risk factors that are most frequently seen are hypertension, smoking, and family history.
Alcohol, sympathomimetic drugs, and a lack of estrogen are other risk factors [24]. In the present study, we analyze
these modifiable risk factors which might have a correlation in the outcome of these group of patients with aSAH.
Based on the table, around 45% of the patients are smokers while 48.4% of them are non-smokers. Moreover, about
53.3% of the non-smokers have died due to aSAH but only 35.7% of the current smokers have died due to aSAH.
This may suggest that smoking is not associated with deaths due to aSAH. This is confirmed by the results of the
Fisher’s exact test (p-value = 0.725). Therefore, at a 5% significance level, there is no sufficient evidence to say that
smoking increases the risk of death due to aSAH. This is also true with the study done by S. Chotai et. al. wherein
they stated that in this cohort of young individuals, smoking history was not found to be a predictor of bad outcomes
[3].
Furthermore, about 42% of the patients have hypertension and two patients have diabetes mellitus. It is clear from
the table that the death rate of patients without comorbidities is lower than those with comorbidities. However, the
result of the Fisher’s sign test (p-value = 0.727) concludes that there is no significant relationship between the
presence of comorbidities and mortality due to aSAH. The result of this study is again supported by the study done
by S. Chotai et. al. wherein they found out that the history of hypertension was not significantly associated with the
outcome at discharge of young adults with aneurysmal subarachnoid hemorrhage. However, they added that the
history of hypertension was a significant predictor of the outcomes at mean 2-year follow up [3].
On a short note, none of the patients have a family history of aSAH. Thus, this study cannot conclude whether
family history is associated with deaths due to aSAH or not.
In this study, anterior communicating artery aneurysms were found in 12 out of 31 patients followed by middle
cerebral artery aneurysms in 6 out of 31 patients. This is the same as with the general population wherein the
anterior communicating artery (30%) is the most common location of intracranial aneurysm [9]. This is in contrast
with the study done by S. Choitai et. al. (2013), wherein they found out that the ACA (47.2%) was the most
common site in young adults [3].
Eighty-five percent (85%) of aneurysmal SAH cases are caused by saccular (berry) aneurysms, the majority of
which originate from the circle of Willis and occur in the anterior circulation. Additionally, cerebral aneurysms are
typically solitary (70% to 75%) but may be multiple (25% to 50%) in some cases. [9]. In this study, 15 of the
classified aneurysms were saccular, 16 have solitary aneurysm and only 2 patients have multiple aneurysms. This is
similar to that seen in the general population as mentioned above.
Based on the results of the Fisher’s exact test, location, type, and the number of aneurysms is not associated with the
mortality of the patients with aSAH. This result is again similar with the study done by S. Chotai et. al. (2013),
specifically in terms of the location of the aneurysm wherein they concluded that the location of aneurysm was not
found to be a significant predictor of outcomes for these group of patients with aSAH [3].
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Meanwhile, most of the patients have a Hunt and Hess (HH) score of 1 (38.7%) upon presentation. Moreover, all of
those patients with HH scores of 4 and above have died due to aSAH. The survival rate decreased from 66.6% for
patients with HH scores of 1 to 0% for patients with HH scores of 4 and 5. Using Fisher’s exact test confirms the
relationship between HH score and the mortality of patients with a p-value of 0.019. Particularly, patients with
higher HH scores have a lower chance of surviving than those with lower HH scores. This is why until now, the
Hunt and Hess scoring system which is used to classify the severity of a subarachnoid hemorrhage based on the
patient’s clinical condition is also used as a predictor of prognosis/outcome with a higher-grade correlating to a
lower survival rate [14].
In addition, most of the patients have an MFG score of 4 (31.8%) followed by patients with an MFG score of 1
(27.3%). All the patients with MFGS of 1 survived while more than half of the patients with MFGS of 4 did not
survive. This might be an indication that higher MFGS leads to lower survival rates, but the result of Fisher’s exact
test says otherwise. With a p-value of 0.113, there is insufficient evidence to claim that MFGS is associated with the
mortality of patients with aSAH. This is in contrast with the results of the study done by Martin et. al (2021).They
concluded that both grading systems are highly correlated with clinical outcome. Increasing Fisher grade was highly
correlated with poor outcome and with mortality. However, they also added that the modified Fisher grading system
has a higher index of inter-rater agreement [26].
In addition, the current study may also be elevated to a larger area of conduct by having patients from other hospitals
within the target location as part of the population. This is expected to yield a more diverse result for the study itself.
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Appendices
Table 3:- Hunt and Hess Grading and Predictive Mortality from subarachnoid Hemorrhage (14).
Grade Characteristics Mortality Rate (%)
0 Unruptured aneurysm without 0
symptoms
1 Asymptomatic or minimal headache 1
and slight nuchal rigidity
1a No acute meningeal or brain reaction 1
but with fixed neurological deficit
2 Moderate to severe headache, nuchal 5
rigidity, no neurologic deficit other
than cranial nerve palsy
3 Drowsy, confused, or mild focal 19
deficit
4 Stupor, moderate to severe 42
hemiparesis, possibly early
decerebrate rigidity, and vegetative
disturbances
5 Deep coma, decerebrate rigidity, 77
moribund
Table 4:- Modified Fischer Grade Score and Risk for Delayed Cerebral Ischemia [15].
Modified Fischer Grade Score CT scan Findings Risk for DCI (%)
0 No SAH or IVH 0
1 Minimal/thin SAH, no IVH 6
2 Minimal/thin SAH, with IVH in both lateral 15
ventricles
3 Dense SAH, no IVH 34
4 Dense SAH, with IVH on both ventricles 35
419