REVISTA MÉDICA DE LA UNIVERSIDAD DE COSTA RICA
Volumen 16, Número 1, Artículo 2 Abril-Octubre 2022
ISSN: 1659-2441 Publicación semestral www.revistamedica.ucr.ac.cr
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
15
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
INVESTIGACIÓN ORIGINAL
PRESTACIÓN DE ATENCIÓN MÉDICA, FACTORES DE
RIESGO CARDIOVASCULAR Y HEMORRAGIA
INTRACEREBRAL ESPONTÁNEA EN LA POBLACIÓN
COSTARRICENSE
DELIVERY OF HEALTHCARE, CARDIOVASCULAR RISK
FACTORS, AND SPONTANEOUS INTRACEREBRAL
HEMORRHAGE IN COSTA RICAN POPULATION
Rosales Bravo, Luis
Department of Anatomy and Clinical Department Hospital México, School of Medicine, University of Costa Rica, San
Pedro de Montes de Oca, San José, Costa Rica. ORCID ID: https://orcid.org/ 0000-0002-0259-0476. Correo:
luis.rosalesbravo@ucr.ac.cr
RESUMEN: Costa Rica es un país pequeño con una economía emergente con un gobierno democrático que no
tiene ejército. Su sistema de salud es uno de los más eficientes del mundo y es el país latinoamericano con
mayor esperanza de vida. Sin embargo, los factores de riesgo cardiovascular afectan cada vez más a esta
población. El objetivo de este estudio fue revisar la prestación de atención médica, así como los principales
factores de riesgo cardiovascular en la población costarricense y su relación con la hemorragia cerebral
espontánea. Estos factores de riesgo se relacionan con el desarrollo de hemorragia intracerebral espontánea
y, además, cabe mencionar que hay poca información científica en este país que relacione estas dos
condiciones. De esta manera, se realizó una búsqueda actualizada en la base de datos PubMed (MeSH y DeCS)
y se seleccionaron 79 artículos científicos. Se buscaron referencias adicionales en la base de datos del autor.
Se concluye que la población costarricense posee una mayor exposición y vulnerabilidad a la hemorragia
intracerebral espontánea, esto debido a la alta prevalencia de factores de riesgo cardiovascular en este grupo
y a una mayor esperanza de vida.
Palabras clave: prestación de atención médica, hipertensión, fumado, obesidad, hemorragia cerebral.
Fuente: DeCS, BIREME.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
16
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
Recibido: 9 Enero 2022. Aceptado: 20 Febrero 2022. Publicado: 20 Abril 2022.
DOI: https://doi.org/10.15517/RMUCRV1611.50835
ABSTRACT: Costa Rica is a small country with an emerging economy and a democratic government, that
does not have an army. Its healthcare system is one of the most efficient systems around the world. It is the
Latin American country with the highest life expectancy. Nevertheless, cardiovascular risk factors
increasingly affect this population. The goal of this study is to review the delivery of healthcare and the main
cardiovascular risk factors in the Costa Rican population and its relationship with spontaneous intracerebral
hemorrhage. These risk factors are related to the development of spontaneous intracerebral hemorrhage.
There is little scientific information -in this country- that relates to these two conditions. Therefore, an
updated research was carried out in the PubMed database (MeSH and DeCS) 79 articles were selected. We
also searched for additional references in the author's database. Regarding conclusions, Costa Rican
population has increased vulnerability to develop spontaneous intracerebral hemorrhage due to the high
prevalence of cardiovascular risk factors and because of the longer life expectancy.
Key words: delivery of health care, hypertension, smoking, obesity, cerebral hemorrhage. Source: DeCS,
BIREME.
INTRODUCTION
Located in Central America, Costa Rica is a small
country with 51.100 km2 (1, 2), divided into seven
small departments (provinces). It has no army and
has a democratic government system. Costa Rica
has one of the most efficient health systems
globally and has the highest life expectancy in Latin
America (3). One of the 5 Blue Zones, Península de
Nicoya, is located in Costa Rica (shown in Figure
No. 1).
Figure No. 1. Geographic location of Costa Rica in
the World map. Costa Rica is located in Central
America. The dark area shows the Blue Zone,
Península de Nicoya.
In these zones, the people consistently live for
more than 100 years. Besides, the whole
population is aging at a rapid pace. It is expected
that the number of people with age of 60 years old
and over will double from year 2000 to 2025.
The lifestyles of Costa Ricans have changed in the
last years, especially feeding habits. Many
cardiovascular risk factors make this population
vulnerable to develop cerebrovascular disease
(CVD). This is particularly true for spontaneous
intracerebral hemorrhage (ICH). Few clinical and
demographic data is available about CVD. This
review's primary goal is to analyze the
cardiovascular risk factors that affect the Costa
Rican population and to link these cardiovascular
risk factors with the potential risk of ICH. Finally, it
has been done concise review of the actual
knowledge regarding ICH.
PUBLIC HEALTH SYSTEM
According to the United Nations Population Fund,
Costa Rica has about 5.1 million citizens (4). It is
considered a developing country with an emerging
economy. Since 1941 it has a very efficient social
healthcare system. In 1961 the legal arrangements
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
17
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
were established so that the healthcare system was
universal and solidary (5). This system covers 85.6
%-87.6 % of the population (citizens and
immigrants)(6). The government finances it by
about 75 % (7). The state invests approximately
9.3 % of the Gross Domestic Product (GDP) on
public healthcare (8).
Because of these reasons, the leading health
indicators (life expectancy, birth rate, fertility rate,
and maternal mortality) are similar to that of
developed countries (shown in Table 1). Special
mention deserves the infant mortality rates, one of
the lowest globally (2, 8).
Table No. 1. Demographics and health indicators
of Costa Rica
Indicator
Value
Area (sq. km)
Population (million citizens)
Life expectancy at birth (years)
Fertility Rate per women
Maternal mortality ratio (deaths per
100.000 live births)
Children under-five mortality rate
(number of deaths per 1000 live births)
Total expenditure on health as % of GDP
In 2004, Costa Rica had a vast network of public
healthcare centers (692), including primary health
care centers (EBAIS for its abbreviation in
Spanish), clinics, and hospitals (9). By 2006 the
government increased the number of EBAIS to 893
(10). By 2011, the country had 947 EBAIS, 11
major clinics, 13 peripheral hospitals, 7 regional
hospitals, 3 third-level hospitals and 4 specialized
hospitals (6).
Half of the Costa Rican population lives less than 1
km from an EBAIS and 5 km from a major clinic or
a hospital (9). In this way, the government
guarantees adequate accessibility to healthcare
services. According to that, hypertensive and
diabetic patients are treated in an EBAIS every four
months and three months, respectively (11).
PRIVATE HEALTH SYSTEM
Similarly, Costa Rica has an extensive private
healthcare system. This system is expanding every
year, increasing the coverage of healthcare for the
population. There are 9 private hospitals in the
national territory (12). Also, there are 468 private
clinics and consulting rooms (13). As claimed by
the Health Expenditure Survey carried out in 2006,
the Costa Rican population has a high preference
for visiting a private healthcare service (14). About
56 % of the population attended a private
healthcare facility, as stated in a survey carried out
by the University of Costa Rica in 2006 (15).
Nearly 50 % of the population would prefer to stop
contributing to the social healthcare and join a
private healthcare system. The main reason is the
long waiting time until an attending physician sees
the patients in the public healthcare system,
according to a report issued by a Government
Agency in 2009 (16).
COSTA RICAN CARDIOVASCULAR RISK
FACTORS
The prevalence of chronic diseases related to
increased cardiovascular risk is very similar to
developed countries, especially compared to the
United States (17). Additionally, there has been a
change in the lifestyle of the communities. This
change has favored an increase in the prevalence
and incidence of cardiovascular and
cerebrovascular disease.
Related to chronic hypertension (HT), one of four
adults is a hypertense patient, a proportion that
increased by 10 % in the last 15 years (18). The
estimated overall prevalence of HT is 25.6 % (19);
in 65 years old and over, it rises to 61 % (10). HT
is the second leading cause of seeking medical care
in outpatient services in public healthcare centers
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
18
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
(10). The mortality rate from high blood pressure
has tended to double in recent years (20).
Regarding Diabetes Mellitus (DM), its overall
prevalence ranges from 6.4 % - 13 % (19, 21-23).
It has an incidence of 1.62 cases per 100.000
inhabitants per year (23). The overall prevalence
of patients with high fasting blood glucose is about
16.5 % (22). Furthermore, it has been determined
that high amounts of the lipid cis-9, trans-11
isomer of linoleic acid in the adipose tissue were
associated with a lower prevalence of diabetes.
Adipose tissue amounts of these isomers were
significantly lower in adults with diabetes than in
adults without diabetes in Costa Rican population
(21).
The prevalence of overweight and obesity ranged
from 59.7 % -77.3 % in the population between
20-64 years of age (24). The urban population has
a higher prevalence of systemic obesity and
abdominal obesity than the rural population,
especially men (25). Both types of obesity are
independently associated with the development of
diabetes, increased risk of CVD, and coronary
artery disease. It is well demonstrated that obesity
causes peripheral resistance to insulin, leading to
hyperglycemia. Insulin resistance causes an
increase in the synthesis of apolipoprotein C-III
(Apo C-III). The ApoC-III leads to an alteration in
the plasma clearance of apo B lipoproteins, which
increases the concentration of triacylglycerol (26).
The increase in both lipoproteins (Apo C-III, Apo B)
is related to a high risk of cardiovascular disease in
Costa Rica since it accelerates and activates the
systemic arteriosclerotic process (26).
Despite that the consumption of trans fatty acids in
the Costa Ricans diet has decreased in recent years,
it remains high (27). Trans-fatty acids are found
mainly in soybean oil and palm oil, which are used
in food preparation. Excess consumption of trans
fatty acids is related to an increased risk of acute
myocardial infarction (27). Replacing palm and
soybean oils with vegetable oils containing
polyunsaturated non-hydrogenated fatty acids
(linoleic acid and α-linoleic acid) could reduce
atherosclerosis and cardiovascular risk in the
country, particularly the risk for heart attack (28).
These polyunsaturated fatty acids reduce LDL-
cholesterol levels, increase peripheral insulin
sensitivity, inhibit platelet aggregation, reduce
systemic blood pressure, and decrease cardiac
arrhythmias (28).
The establishment of fast-food restaurants has
varied the eating habits of consumers. The high
salt content in many foods of these restaurants has
been well demonstrated (29). High salt intake is
related to the development of HT and
cardiovascular disease.
On the other hand, it exists a direct relationship
between smoking and the development of ischemic
CVD—nearly half a million Costa Ricans (13.5 % of
the total population) smoke (30). The smoking
habit begins very early , about the age of 10 years
old (31). Although, the prevalence of smoking
among teenagers between 13-15 years old has
significantly decreased because the public health
policies, the proportion of young people addicted
to smoking has increased (32). It will be more
frequent in this context that the Costa Rican
population suffer from CVD since several
cardiovascular risk factors are exposed.
Approximately 57.1 % of the adult population
reported having had at least one alcoholic drink in
the last 12 months (median incidence). Men report
a greater incidence (67.8 %) than women (46.4 %)
(33). The median age at which regular alcohol
consumption starts is 18 years old in the general
population (33). While a light-to-moderate alcohol
consumption (1-2 drinks/day) decreases the risk
for ischemic stroke, it does not affect hemorrhagic
stroke risk. Heavy alcohol consumption (>4
drinks/day) is associated with a statistically
significant (CI 95%, p <0.05) increase in the risk of
all types of stroke: Ischemic stroke (RR 1.14),
intracerebral hemorrhage (RR 1.67), and
subarachnoid hemorrhage (RR 1.82). The most
noticeable effect in risk increase being in
hemorrhagic stroke (34). The most significant risk
for alcohol abuse among the Costa Rican
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
19
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
population is for men, ages 25-34 years old, who
live in the Great Metropolitan Area. According to
the Public Ministry of Health, 28 % of the people
who regularly consume alcohol report heavy
alcohol consumption (33).
SPONTANEOUS INTRACEREBRAL
HEMORRHAGE
ICH represents around 20 % of CVD. Spontaneous
ICH refers to a non-traumatic brain bleeding
caused by a ruptured cerebral artery or vein. This
hemorrhage can be located in three different
anatomical sites: intracerebral (intraparenchymal),
intraventricular, or both. The most frequent is the
parenchymal hemorrhage (shown in Figure No. 2).
Figure No. 2. Non-contrast axial brain-CT
This figure shows hyperdense lesion (bleeding) located
at the level of the left putamen. Also, some degree of
compression of the anterior and posterior horn of the
left lateral ventricle are observed. There are some shift
of the middle line to the contraleral side.
About 60 % of ICH are secondary to HT (sudden
increase in blood pressure), 20 % to amyloid
angiopathy and the remaining 20 % are secondary
to various causes as oral anticoagulants (OA), brain
tumors, use of anticoagulants, vascular
malformations (dural fistulas, arteriovenous
malformations), and rupture of brain aneurysms.
ICH is one of the most devastating CVD subtypes. It
is associated with high mortality, close to 40 %
during the first 30 days (35). A high proportion of
patients die in the first two days. Only between 12
% -39 % of patients achieve long-term functional
independence (36).
The early death rate is higher in older adults,
females with history of HT, and OA (37). Contrary,
the factors associated with a lower mortality rate
are hypothyroidism and obesity (38). Those
patients that survive usually persist with severe
neurological deficits.
Frequently many of these patients are readmitted
to the hospital because of various medical and
surgical complications, which include: sodium
concentration disturbance, venous
thromboembolism, lung infections, gastrostomy
dysfunction, external ventriculostomy and history
of craniotomy (39).
The glycemic level also influences the clinical
prognosis in this group of patients, particularly in
the post-event stage. Hyperglycemia is a response
to acute stress caused by cerebral hemorrhage. It
has been associated with increased hematoma
volume, more significant neurological damage, and
worse clinical evolution (40). Transient
hyperglycemia can cause brain damage through
complex neuro-inflammatory mechanisms
(cytokines, oxidative stress, and calcium
metabolism) (41, 42).
RISK FACTORS IN ICH
The main risk factor related to ICH is HT. Sustained
hypertension causes degenerative changes in the
wall of the small cerebral arteries. These changes
consist mainly of fibrinoid necrosis of the sub-
endothelium with the formation of
microaneurysms and focal ectasias, which weaken
the arterial wall (36). Such arterial
microaneurysms are known as Charcot-Bouchard.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
20
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
The normal circadian rhythm causes a 10-20 %
reduction in blood pressure during sleep and
constitutes a cardiovascular system's protective
mechanism. In hypertensive patients, this
mechanism is lost, and contrary, they present a
nocturnal increase in blood pressure. These can
result in endothelial dysfunction, remodeling of the
small cerebral arteries, and affect hypertensive
patients (43).
The second most important risk factor is cerebral
amyloid angiopathy (CAA) (44). It is the deposition
of β-amyloid in capillaries, arterioles, and small
and arteries in the cerebral cortex, leptomeninges,
and cerebellum (45). Typically, β-amyloid is
involved in the reduction of cellular oxidative
stress and the regulation of cholesterol transport
(46). This macro protein excessive deposition in
the arterial walls leads to the small cerebral
perforating arteries rupture (47).
Apolipoprotein E (ApoE) contributes to the cellular
behavior of β-amyloid, which is also an essential
component of arterial atheroma plaques. The
polymorphism of the gene that encodes for Apo E
synthesis is linked to an increased ICH risk. The
ApoE gene is located on chromosome 19 and
encodes a lipoprotein composed of 299 amino
acids. A recent meta-analysis reported that the ε4
and ε2 alleles' polymorphism are risk factors for
ICH, mainly in white patients (48).
Diabetic patients have a 3-4 times higher risk of
having ICH compared to non-diabetics. DM induces
angiopathy (thickening of the basement membrane
of the small cerebral arteries and proliferation of
the endothelium) (41). DM is a risk factor for
atherosclerosis, which harms the
microvasculature. The former causes a condition
known as diabetic microangiopathy (41, 42). This
explains why diabetic patients are more likely to
suffer ICH.
The use of oral anticoagulants (OA) is another risk
factor related to ICH. OA can be of two types:
antiplatelet agents (aspirin, clopidogrel,
dipyridamole, ticagrelor) and anticoagulants
(warfarin, rivaroxaban, dabigatran, apixaban).
These medications can be prescribed as
monotherapy (aspirin only) or in combinations
(warfarin plus aspirin). They are mainly used as a
treatment for the primary and secondary
prevention of thrombotic events. Recently, was
demonstrated that the combined use of warfarin +
aspirin + clopidogrel was associated with an
increased risk of having ICH (49). Those patients
who had ICH due to the use of warfarin had higher
90 days' mortality. The OA associated with a lower
risk of ICH was dabigatran (49).
Age is a non-modifiable risk factor. This disease is
more prevalent in people older than 65 years.
However, the population group younger than 50
years (range 18-50) could be affected. HT is also
the leading risk factor in this age group (50).
Air pollution is linked to an increased likelihood of
ICH. Microparticles levels on air bigger than 77.45
µg/m3 correlate with a greater probability of
having ICH, especially in those over 65 years of age
and diabetics (51). Exposure to these toxic
microparticles in the air in experimentally
observed humans and animals allowed for the
documentation of hemostatic alterations, systemic
inflammation, damage to the capillary endothelium
and vascular dysfunction (51).
High alcohol consumption is a risk factor for ICH.
High consumption is considered 40> g/d or> 300
g/week. Patients with high alcohol consumption
who have ICH compared to non-alcoholics are 11
years younger, have a smoking habit, have a worse
prognosis and the bleeding' location is mainly in
the posterior fossa (52). Patients with alcoholic
cirrhosis, mainly men aged between 20-49 years,
have a high risk of ICH (53). The development of
cirrhosis in this group of patients causes significant
disorders in blood coagulation (hemorrhagic
diathesis), alters the autoregulation of cerebral
blood flow, and promotes HT's development (53).
Although smoking increases the risk of ischemic
stroke and subarachnoid hemorrhage, it is not
identified as a risk factor for ICH (54). Its effect on
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
21
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
the functional outcome of patients with
spontaneous ICH is on debate. Preclinical ICH
models associate the stimulation of the a7-
nicotinic acetylcholine receptor (a7-nAChR) and its
anti-inflammatory effect with improved
neurological outcomes (55). However, recent
clinical studies have shown no significant
difference in functional outcome at 90 days
between non-smokers and current smokers. The
same was found between recent smokers (30 or
fewer days) and non-recent smokers, measured by
the modified Rankin Scale (mRS) and Barthel Index
(55). Other study found no difference in the long
term functional outcome (mRS at 12 months)
among spontaneous ICH patients with only
nicotine use and patients without legal drug use
(alcohol and or nicotine) (56). Furthermore,
smoking is associated with an earlier age of ICH
presentation and increased ICH-related mortality
in former or current smokers compared to non-
smokers (55). This suggests that the harmful
effects of smoking on the overall health outcomes
outweigh the probable neuroprotective effects of
nicotine (55). Low serum LDL-Cholesterol levels
<70 mg/dl and triglycerides <74 mg/dl have been
linked to an increased risk of ICH (57, 58). This
increased risk is related to necrosis and weakening
of the arterial wall's middle tunic, which alters the
endothelium, making it more susceptible to
microaneurysms (58).
NEUROIMAGING
The study of choice to evaluate extension, location,
and volume of ICH is a non-contrast brain CT. It is a
quick study to perform with high sensitivity to
diagnose patients in which intracranial
hemorrhage is considered (47, 59). An
intracerebral hematoma (IH) volume of ≤ 30 ml is
considered a small extent, and one of ≥30 ml is
regarded as a great extension. The latter is related
to higher morbidity and mortality (60).
The growth of IH is very common. It can be
observed within the first 24 hours after symptom
onset but predominantly occurs in the early hours
(61). Approximately 15-23 % of patients present
hematoma expansion in the first several hours
(47). Hematoma growth causes the patient's
neurological deterioration, poor outcome, and
death (62). IH expansion occurs in about 70 % of
ICH patients and is more likely to happen in those
cases with an initial hematoma volume ≥30 ml
(61).
The measure of the IH volume is very important
both to take urgent treatment decisions (surgical
evacuation) and to define the clinical prognosis
(47, 63). To date, the most common way to
calculate this volume is by using the ABC/2
method (measures of the maximum diameter (in
mm) of the hematoma in the perpendicular, axial
and coronal planes are multiplied by each other
and then divided by 2 (47). Although, it is a quick
method and provides an approximate idea of the
hematoma volume, it is highly dependent on who
reports the CT-scan. A recent study compared the
ABC/2 method, sABC/2 (a simplified version) with
the planimetric form. It suggested that while both
are accurate instruments to calculate the volume of
the hematoma (demonstrated by concordance with
the planimetric method), sABC/2 showed less bias
and may be more sensitive in differentiating a
volume threshold of 30mL (63).
With the new CT-scan software named
Convolutional Neuronal Network (CNN), 3D
quantification and automatic segmentation
techniques to measure the IH could be done. This
technique gives a more accurate volume of IH (64).
To predict by the initial brain CT-scan which one is
more likely to have a hematoma growing (an
increase of more than 33 % in size or > 6 ml in
volume), various protocols and scales have been
designed. One of these scales assigns a maximum
score of 10 based exclusively on the initial brain
CT-scan. This scale is mainly based on IH's initial
volume and its tomographic morphological
characteristics (65). The presence of the "spot
sign" in the initial angio brain-CT is closely
correlated with an increase and expansion of IH
(66). Both diagnostic methods can contribute to
the early identification and treatment of this group
of patients.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
22
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
Another predictor of IH expansion is the
differential count of white blood cells. A marked
inflammatory process occurs quickly when the
when the ICH begins. This causes the migration of
leukocytes around the lesion due to the disruption
of the blood-brain barrier (BBB). There is an
imbalance between procoagulant substances
(stabilize the hematoma) and anticoagulant
substances (favor hematoma expansion) in the
bleeding site. In a recent study, it was observed
that the increase in the eosinophil count (45 cells /
µL) in the incoming leukogram is directly
associated with the IH growing, particularly if it
has a volume> 30 ml (35). It is not yet clear how
eosinophil activity contributes to this
phenomenon.
The extension of the IH to the ventricular system
occurs often. Hypertensive bleeding (located in the
basal nuclei and thalamus) frequently drains into
the third ventricle or the lateral ventricles. The
bleed may cause a slowing or obstruction of the
cerebrospinal fluid (CSF) circulation leading to
obstructive hydrocephalus. These may lead to an
increase of intracranial pressure with a worsening
of the patient's neurological state. Bleeding at the
level of the head of the caudate nucleus causes
extension of bleeding into the lateral ventricles, too
(shown in Figure No. 3) (67).
MEDICAL MANAGEMENT
General measures of ICH management include
basic ABC: securing the airway (endotracheal
intubation if necessary), ensuring oxygenation, and
maintaining adequate blood pressure. Also,
glycemic levels should be kept below 140 mg/dl,
avoid hyperthermia, and keep sufficient blood
volume using isotonic solutions. It is also essential
to prevent deep vein thrombosis of the lower limbs
with antithrombotic prophylaxis. Additionally, it is
vital to guarantee adequate parenteral nutrition
because of the high energy expenditure of this kind
of patient (68).
More than 70% of patients with ICH are admitted
with systolic blood pressure (SBP) higher than >
140 mmHg. The increase in SBP is related to IH
growing during the first 24 hours. The intensive
reduction of SBP to maintain it lower than <140
mmHg during the first hour of admission is safe for
the patient. This reduces the possibility of IH
growing without compromising cerebral perfusion
in the perihematomal area (69).
Figure No. 3. Non-contrast axial brain-CT
Non-contrast axial brain-CT shows hyperdense lesion
(bleeding) located at the level of the head of the right
caudate nucleus causing extension of the bleeding
mainly into the right lateral ventricles (anterior and
posterior horns). Some degree of bleeding is also
observed into the left lateral ventricles and the third
ventricle.
Extravasation of blood into the brain parenchyma
promotes the onset of an active inflammatory
process. This causes a significant cytotoxic and
vasogenic edema around the IH. This process leads
to a disruption of the BBB. The disruption of the
BBB generates the migration of more inflammatory
cells. The inflammatory process can last up to 21
days. Microglia, astrocytes, and T lymphocytes are
the primary cells involved in the perilesional
edema (70).
Experimentally in animal models, some drugs have
been studied to reduce the neuroinflammatory
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
23
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
process related to ICH. Hypoglycemic agents of the
thiazolidinedione group (Rosiglitazone) could
reduce the pro-inflammatory factors produced by
microglia. Tetracyclines (minocycline) could
reduce the concentrations of metalloproteinases
and TNF-α. Finally, fingolimod a sphingosine-1
receptor modulator that prevents the migration of
active T lymphocytes to the central nervous system
has been also tested (71).
Statins (atorvastatin, simvastatin) are drugs used
in both acute and post-ICH management. Such
drugs have been shown to have various
neuroprotective effects in both animal and human
experimental studies. These effects include
improving neurological function, reducing cerebral
edema, an increase of angiogenesis and
neurogenesis, reabsorption of the hematoma, and
reducing inflammatory cells (72).
Special mention deserves those cases of ICH
secondary to oral anticoagulants. In the case of
warfarin, reverse anticoagulation with vitamin K
10 mg IV and prothrombin complex concentrate
(30 IU / kg) during the first 4 hours. The goal is to
bring the INR lower than <1.2. (75). For thrombin
inhibitors (dabigatran), their effect should be
reversed with the monoclonal antibody
idarucizumab (Praxbind®) at a single dose of 5
grams IV. For factor Xa inhibitors, modified
recombinant factor Xa (andexanet alfa) should be
administered IV (73).
The controversy arises in those cases in which
patients with ICH need to be anticoagulated
because of a particular medical condition (e.g.,
mitral or aortic valve replacement, AF). Special
conditions which could increase the risk to present
cerebral or peripheral thromboembolic
complications. The doubt arises if by normalizing
the INR and starting IV anticoagulation with
heparin sodium, there will be a significant risk of
rebleeding ending up with IH growing. Current
evidence supports IV heparin treatment (TPT
prolongation 1.5-2 times) after INR normalization
in patients with ICH requiring urgent
anticoagulation. Depending on the patient's
neurological condition and functional prognosis, it
may be considered to restart OA two weeks after
ICH (74).
Due to immobilization caused by neurological
deficits (hemiparesis), the DVT risk could be as
high as 70 %. The lower limb's immobility causes
slowing of the venous return and a
hypercoagulable state in this vascular territory.
DVT is the leading risk factor for developing PTE.
DVT is a severe complication that increases
morbidity and mortality. Therefore, preventing
DVT is an essential part of medical treatment.
Prophylactic doses of fractionated heparin (sodium
heparin) or LMWH (enoxaparin) can be started
since the second day of admission with this
purpose. This neither increases the risk of brain
rebleeding nor neurological deterioration (75).
Finally, patients who need a platelet antiaggregant
(aspirin) to prevent cardiovascular events use
aspirin two weeks after ICH is safe. This neither
increases the risk of mortality nor disability (76).
SURGICAL TREATMENT
Most patients with ICH do not require brain
surgery. Sometimes the anatomical location and
volume of the IH could be a life-threatening
condition. The mechanisms that can lead to this are
mass effect, herniation of intracranial structures,
sudden increase of intracranial pressure, and
abrupt blockage of CSF (shown in Fig. 4)
excitotoxic/neurotoxic effect of blood degradation
products.
Theoretically, there is a benefit of surgical drainage
of the IH. Among the surgical modalities available
are open craniotomy, decompressive craniectomy,
neuroendoscopy, minimally invasive catheter-
guided hematoma evacuation, external
ventriculostomy, and placement of a ventricular-
peritoneal shunt (77).
Despite these surgical procedures and after many
clinical studies in this regard, to date, the benefit of
surgical evacuation of the IH has not been well
established when compared with the best medical
treatment. An exception are patients who have a
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
24
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
hemorrhage in the posterior fossa with acute
hydrocephalus, compression of the brain stem, and
a decline in their neurological condition. In such
cases, surgical intervention can save their lives but
does not necessarily reduce overall patient
mortality. But suppose the medical center where
these procedures are performed (particularly open
craniotomy) does many of these surgeries per
year. In that case, this may favor the clinical
prognosis, given that the learning curve has been
increased (78).
Figure No. 4. Non-contrast axial brain-CT
Non-contrast axial brain-CT shows hyperdense lesion
(bleeding) located at the level of the pons compressing
the Silvio aqueduct. These compression causes blockage
of the CSF leading to acute hydrocephalus. Both
posterior horns of the lateral ventricles are enlarged.
CONCLUSION
This review has described the relationship
between the delivery of healthcare, cardiovascular
risk factors, and ICH in the Costa Rican population.
Despite being a small country, Costa Rica has one
of the most efficient healthcare systems
worldwide. It has an extensive network of both
public and private care services. This allows having
excellent leading health indicators, particularly a
long-life expectancy and low infant mortality rates.
Therefore, the proportion of patients older than 60
years tends to increase gradually.
The prevalence of chronic diseases related to
cardiovascular risk, greater life expectancy, eating
habits, and Costa Rican population lifestyles make
them increasingly prone to cardiovascular
diseases, including ICH. Scarce information is
available about the prevalence and incidence of
ICH in this country. In a recent descriptive study,
the prevalence of hemorrhagic CVD was 20.5 %,
being HT, DM, and dyslipidemia, the three most
common risk factors founded (79).
Despite the above, Costa Rican population is
similarly exposed to cardiovascular risk factors
related to ICH development than the global level.
Most of these factors have been studied in this
population, such as HT, DM, overweight/ obesity,
eating habits, smoking, and alcoholism. No
scientific information could be found on OA's use,
air pollution, and risk of ICH in the Costa Rican
population. More studies are required about these
topics. This review aimed to contribute to
encourage the government to create policies to
reduce and control cardiovascular risk factors
related to ICH.
Finally, more local clinical studies in the field of
ICH are needed to obtain information about
incidence, prevalence, clinical course, mortality,
complications and readmission rates.
ACKNOWLEDGEMENTS
The author wishes to thank Ellen Sánchez-Más, MD
for the exhaustive review of the manuscript and
Mr. Esteban Rodríguez Ortiz from Digital
Animation® for the design of Figure No. 1.
COMPETING INTERESTS
The author declare that no competing interests
exist.
FUNDING
Not applicable.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
25
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
BIBLIOGRAPHY
1. Bank TW. Surface area (sq.km) - Costa Rica. Consulted: Feb
17, 2021. Available from:
https://data.worldbank.org/indicator/AG.SRF.TOTL.K2?locat
ions=CR.
2. UNICEF. Costa Rica. Key demographic indicators.
Consulted Feb 20, 2021. Available from:
https://data.unicef.org/country/cri/.
3. Rosero-Bixby L. Socioeconomic Development, Health
Interventions and Mortality Decline in Costa Rica. Scand J Soc
Med Suppl. 1991 Nov;46:33-42.
4. Fondo de Población de las Naciones Unidas. Población
mundial. Costa Rica. Consulted: Mar 3, 2021. Available from:
https://www.unfpa.org/es/data/world-population-
dashboard.
5. Mesa-Lago C. Health care in Costa Rica: boom and crisis.
Soc Sci Med. 1985 Feb;21(1):13-21.
6. Saénz M AM, Muiser J, Bermúdez J. Sistema de salud de
Costa Rica. Salud Publica Mex. 2011 Mar;53(2):S156-S167.
7. Morera Salas M, Aparicio Llanos A. Determinants of health
care utilization in Costa Rica. Gac Sanit. 2010 Oct;24(5):410-
415.
8. Dow WH, Schmeer KK. Health insurance and child
mortality in Costa Rica. Soc Sci Med. 2003 Sep;57(6):975-
986.
9. Rosero-Bixby L. Spatial access to health care in Costa Rica
and its equity: a GIS-based study. Soc Sci Med. 2004
Apr;58(7):1271-1284.
10. Cerdas M. Epidemiology and control of hypertension and
diabetes in Costa Rica. Ren Fail. 2006 Jul;28(8):693-696.
11. Fort MP, Alvarado-Molina N, Pena L, Mendoza Montano C,
Murrillo S, Martinez H. Barriers and facilitating factors for
disease self-management: a qualitative analysis of
perceptions of patients receiving care for type 2 diabetes
and/or hypertension in San Jose, Costa Rica and Tuxtla
Gutierrez, Mexico. BMC Fam Pract. 2013 Sep;14:131.
12. Hospitales ACd. Directorio Hospitales. 2020. Consulted:
Mar 3, 2021. Available from: https://ach.sa.cr/directorio.
13. Hulihealth. Directorio Hospitales y Clínicas 2020.
Consulted: Mar 5, 2021. Available from:
https://www.hulihealth.com/es/clinic.
14. Informe Final Encuesta sobre Gastos en Salud mayo 2006.
Consulted: Mar 6, 2021. Available from:
https://ccp.ucr.ac.cr/documentos/farmacoeconomia/Docum
entos_ENGAS/Encuesta_Gastos_en_Salud_2006.pdf.
15. Encuesta Nacional de Salud (ENSA) Costa Rica, 2006.
Consulted: Mar 6, 2021. Available from:
https://ccp.ucr.ac.cr/documentos/farmacoeconomia/Docum
entos_ENSA/ENSAPresentacionenPDF.pdf.
16. Defensoría de los Habitantes. Informe Anual de Labores
2008-2009. Cuarto Observatorio de Derechos Humanos.
Consulted: Mar 10, 2021. Available from:
http://www.dhr.go.cr/transparencia/informes_institucional
es/informes/labores/documentos/if2008_09.pdf.
17. Miranda JJ, Herrera VM, Chirinos JA, Gomez LF, Perel P,
Pichardo R, et al. Major Cardiovascular Risk Factors in Latin
America: a Comparison with the United States. The Latin
American Consortium of Studies in Obesity (LASO). PLoS
One. 2013 Jan;8(1):e54056.
18. Ministerio de Salud. Plan Nacional para la Reducción del
Consumo Sal/Sodio en la Población de Costa Rica 2011-2021.
Consulted: Mar 10, 2021. Available from:
https://www.ministeriodesalud.go.cr/index.php/biblioteca-
de-archivos/sobre-el-ministerio/politcas-y-planes-en-
salud/planes-en-salud/1103-plan-nacional-para-la-
reduccion-del-consumo-de-sal-sodio-en-la-poblacion-de-
costa-rica-2011-2021/file.
19. Organización Panamericana de la Salud. Encuesta sobre
diabetes, hipertensión y factores de riesgo de las
enfermedades crónicas: Centroamérica. 2020 Consulted: Mar
12, 2021. Available from:
https://www.paho.org/hq/index.php?option=com_content&
view=article&id=3070:2010-survey-on-diabetes-
hypertension-chronic-disease-risk-factors-central-
america&Itemid=1353&lang=es.
20. Castillo L, Sánchez M, Alvarado A. Enfermedad
Cardiovascular en Costa Rica. Rev Costarric Salud Pública.
2006 Jul;15(28):1-16.
21. Castro-Webb N, Ruiz-Narvaez EA, Campos H. Cross-
sectional study of conjugated linoleic acid in adipose tissue
and risk of diabetes. Am J Clin Nutr. 2012 Jul;96(1):175-181.
22. Wong-McClure R, Gregg EW, Barcelo A, Sanabria-Lopez L,
Lee K, Abarca-Gomez L, et al. Prevalence of diabetes and
impaired fasting glucose in Costa Rica: Costa Rican National
Cardiovascular Risk Factors Survey, 2010. J Diabetes. 2016
Sep;8(5):686-692.
23. Hasbum B. Epidemiología de la diabetes en Costa Rica. Av
Diabetol. 2010 Apr;26(2):91-94.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
26
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
24. Organización Panamericana de la Salud. Encuesta
Nacional de Nutrición Costa Rica, 2008-2009. Consulted: Mar
12, 2021. Available from: https://www.paho.org/costa-
rica/index.php?option=com_docman&view=download&categ
ory_slug=alimentacion-y-nutricion&alias=67-encuesta-
nacional-de-nutricion-costa-rica-2008-2009&Itemid=222.
25. Campos H, Bailey SM, Gussak LS, Siles X, Ordovas JM,
Schaefer EJ. Relations of body habitus, fitness level, and
cardiovascular risk factors including lipoproteins and
apolipoproteins in a rural and urban Costa Rican population.
Arterioscler Thromb. 1991 Aug;11(4):1077-1088. .
26. Ruiz-Narvaez EA, Sacks FM, Campos H. Abdominal obesity
and hyperglycemia mask the effect of a common APOC3
haplotype on the risk of myocardial infarction. Am J Clin Nutr.
2008 Jun;87(6):1932-1938.
27. Baylin A SX, Donovan A, Fernández X, Campos H. Fatty
acid composition of Costa Rican foods including trans fatty
acid content. J Food Compos Anal. 2007 May;20(3-4):182-
192.
28. Kabagambe EK, Baylin A, Ascherio A, Campos H. The type
of oil used for cooking is associated with the risk of nonfatal
acute myocardial infarction in Costa Rica. J Nutr. 2005
Nov;135(11):2674-2679.
29. Heredia-Blonval K, Blanco-Metzler A, Montero-Campos M,
Dunford EK. The salt content of products from popular fast-
food chains in Costa Rica. Appetite. 2014 Dec;83:173-177.
30. Solís Y, Monge T. Consumo de tabaco en Costa Rica,
relación con múltiples patologías e importancia de la
cesación de fumado. Rev Médica Costa Rica. 2016 Apr;
83(619):285-289.
31. Bejarano J. El consumo de tabaco en la población joven
costarricense. Hallazgos de la encuesta mundial sobre tabaco
en jóvenes. Rev Costarric Salud Pública. 2001 Jul;10(18-
19):19-25.
32. Fonseca-Chaves S, Mendez-Munoz J, Bejarano-Orozco J,
Guerrero-Lopez CM, Reynales-Shigematsu LM. Smoking
tobacco in Costa Rica: susceptibility, consumption and
dependence. Salud Publica Mex. 2017 Mar;59(1):30-39.
33. Ministerio de Salud. Patrones de consumo y consumo
excesivo de bebidas alcohólicas en CostaRica. San José, marzo
de 2010. Mayo 2020. Consulted: Mar 22, 2021. Available
from:
https://www.ministeriodesalud.go.cr/gestores_en_salud/co
msumo_alcohol/costa_rica_patrones_de_consumo_12marzov
3.pdf.
34. Larsson SC, Wallin A, Wolk A, Markus HS. Differing
association of alcohol consumption with different stroke
types: a systematic review and meta-analysis. BMC Med.
2016 Nov 24;14(1):178.
35. Chen Q, Liu J, Xu H, He W, Li Y, Jiao L, et al. Association
Between Eosinophilic Leukocyte Count and Hematoma
Expansion in Acute Spontaneous Intracerebral Hemorrhage.
Front Neurol. 2019 Oct;10:1164.
36. An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and
Clinical Features of Intracerebral Hemorrhage: An Update. J
Stroke. 2017 Jan;19(1):3-10.
37. Al-Khaled M, Awwad S, Brüning T. Nontraumatic
spontaneous intracerebral hemorrhage: Baseline
characteristics and early outcomes. Brain Behav. 2020
Jan;10(1):e01512.
38. Javalkar V, Kuybu O, Davis D, Kelley RE. Factors
Associated with Inpatient Mortality after Intracerebral
Hemorrhage: Updated Information from the United States
Nationwide Inpatient Sample. J Stroke Cerebrovasc Dis. 2020
Mar;29(3):104583.
39. Hoffman H, Furst T, Jalal MS, Chin LS. Annual incidences
and predictors of 30-day readmissions following
spontaneous intracerebral hemorrhage from 2010 to 2014 in
the United States: A retrospective Nationwide analysis.
Heliyon. 2020 Dec;6(1):e03109.
40. Kang K, Lu J, Ju Y, Wang W, Shen Y, Wang A, et al.
Association of pre- and post-stroke glycemic status with
clinical outcome in spontaneous intracerebral hemorrhage.
Sci Rep. 2019 Dec 13;9(1):19054.
41. Herzig R, Vlachova I, Mares J, Gabrys M, Sanak D,
Skoloudik D, et al. Occurrence of diabetes mellitus in
spontaneous intracerebral hemorrhage. Acta Diabetol. 2007
Dec;44(4):201-207.
42. Mankovsky BN, Metzger BE, Molitch ME, Biller J.
Cerebrovascular disorders in patients with diabetes mellitus.
J Diabetes Complications. 1996 Aug;10(4):228-242.
43. Sun J, Yang W, Zhu Y, Liu X, Wei X, Wang B, et al. The
relationship between nocturnal blood pressure and
hemorrhagic stroke in Chinese hypertensive patients. J Clin
Hypertens (Greenwich). 2014 Sep;16(9):652-657.
44. Aguilar MI, Brott TG. Update in intracerebral hemorrhage.
Neurohospitalist. 2011 Jul;1(3):148-159.
45. Kirshner HS, Bradshaw M. The Inflammatory Form of
Cerebral Amyloid Angiopathy or "Cerebral Amyloid
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
27
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
Angiopathy-Related Inflammation" (CAARI). Curr Neurol
Neurosci Rep. 2015 Aug;15(8):54.
46. Kontush A. Amyloid-beta: an antioxidant that becomes a
pro-oxidant and critically contributes to Alzheimer's disease.
Free Radic Biol Med. 2001 Nov;31(9):1120-1131.
47. Dastur CK, Yu W. Current management of spontaneous
intracerebral haemorrhage. Stroke Vasc Neurol. 2017
Feb;2(1):21-29..
48. Nie H, Hu Y, Liu N, Zhang P, Li GG, Li YY, et al.
Apolipoprotein E Gene Polymorphisms Are Risk Factors for
Spontaneous Intracerebral Hemorrhage: A Systematic
Review and Meta-analysis. Curr Med Sci. 2019
Feb;39(1):111-117.
49. Gulati S, Solheim O, Carlsen SM, Oie LR, Jensberg H, Gulati
AM, et al. Risk of intracranial hemorrhage (RICH) in users of
oral antithrombotic drugs: Nationwide
pharmacoepidemiological study. PLoS One. 2018
Aug;13(8):e0202575.
50. Gedansky A, Jarvis P, Yu D, Lu X, Heiman-Patterson T,
Linares G. Intracerebral Hemorrhage in a Young Urban
Population: Etiologies and Outcomes in Patients 50 and
Younger. J Stroke Cerebrovasc Dis. 2019 Oct;28(10):104295.
51. Qian Y, Yu H, Cai B, Fang B, Wang C. Association between
incidence of fatal intracerebral hemorrhagic stroke and fine
particulate air pollution. Environ Health Prev Med. 2019
Jun;24(1):38.
52. Avellaneda-Gomez C, Serra Martinez M, Rodriguez-
Campello A, Ois A, Cuadrado-Godia E, Giralt-Steinhauer E, et
al. Alcohol overuse and intracerebral hemorrhage:
characteristics and long-term outcome. Eur J Neurol. 2018
Nov;25(11):1358-1364.
53. Lin SY, Lin CL, Chen WS, Lin CC, Lin CH, Hsu WH, et al.
Association Between Alcoholic Cirrhosis and Hemorrhagic
Stroke: A Nationwide Population-based Study. Alcohol
Alcohol. 2019 May 1;54(3):302-309.
54. Girot M. [Smoking and stroke]. Presse Med. 2009;38(7-
8):1120-1125.
55. Ironside N, Chen CJ, Pucci J, Connolly ES. Effect of
Cigarette Smoking on Functional Outcomes in Patients with
Spontaneous Intracerebral Hemorrhage. J Stroke
Cerebrovasc Dis. 2019 Sep;28(9):2496-2505.
56. Sembill JA, Sprugel MI, Gerner ST, Beuscher VD, Giede-
Jeppe A, Stocker M, et al. Influence of Prior Nicotine and
Alcohol Use on Functional Outcome in Patients after
Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis. 2018
Apr;27(4):892-899.
57. Rist PM, Buring JE, Ridker PM, Kase CS, Kurth T, Rexrode
KM. Lipid levels and the risk of hemorrhagic stroke among
women. Neurology. 2019 May 7;92(19):e2286-e2294.
58. Ma C, Gurol ME, Huang Z, Lichtenstein AH, Wang X, Wang
Y, et al. Low-density lipoprotein cholesterol and risk of
intracerebral hemorrhage: A prospective study. Neurology.
2019 Jul 30;93(5):e445-e4457.
59. Saad AF, Chaudhari R, Fischbein NJ, Wintermark M.
Intracranial Hemorrhage Imaging. Semin Ultrasound CT MR.
2018 Oct;39(5):441-456.
60. Rost NS, Smith EE, Chang Y, Snider RW, Chanderraj R,
Schwab K, et al. Prediction of functional outcome in patients
with primary intracerebral hemorrhage: the FUNC score.
Stroke. 2008 Aug;39(8):2304-2309.
61. Ovesen C, Havsteen I, Rosenbaum S, Christensen H.
Prediction and Observation of Post-Admission Hematoma
Expansion in Patients with Intracerebral Hemorrhage. Front
Neurol. 2014 Sep 29;5:186.
62. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C,
Krieger D, et al. Guidelines for the management of
spontaneous intracerebral hemorrhage in adults: 2007
update: a guideline from the American Heart
Association/American Stroke Association Stroke Council,
High Blood Pressure Research Council, and the Quality of
Care and Outcomes in Research Interdisciplinary Working
Group. Stroke. 2007 Jun;38(6):2001-2023.
63. Khan M, Baird GL, Elias R, Rodriguez-Srednicki J, Yaghi S,
Yan S, et al. Comparison of Intracerebral Hemorrhage Volume
Calculation Methods and Their Impact on Scoring Tools. J
Neuroimaging. 2017 Jan;27(1):144-148.
64. Patel A, Schreuder F, Klijn CJM, Prokop M, Ginneken BV,
Marquering HA, et al. Intracerebral Haemorrhage
Segmentation in Non-Contrast CT. Sci Rep. 2019 Nov
28;9(1):17858.
65. Fu J, Hu S, Yang M, Li Z, Song X, Wang Z, et al. A Novel 10-
Point Score System to Predict Early Hematoma Growth in
Patients With Spontaneous Intracerebral Hemorrhage. Front
Neurol. 2019 Feb;10:1417.
66. Kim H, Goo JH, Kwak HS, Hwang SB, Chung GH.
Correlation between Spot Sign and Intracranial Hemorrhage
Expansion on Dual-Phase CT Angiography. Diagnostics
(Basel). 2019 Dec;9(4):215.
67. Barnaure I, Liberato AC, Gonzalez RG, Romero JM.
Isolated intraventricular haemorrhage in adults. Br J Radiol.
2017 Jan;90(1069):20160779.
Revista Médica de la Universidad de Costa Rica. Volumen 16, número 1, artículo 2
2022
Revista electrónica publicada por el Departamento de Farmacología de la Escuela de Medicina de la Universidad de
Costa Rica, 2060 San José, Costa Rica. Licensed under a Creative Commons Unported License.
28
Contáctenos al email: revista.medica@ucr.ac.cr Tel: (506) 25-11 4492.
68. Testai FD, Aiyagari V. Acute hemorrhagic stroke
pathophysiology and medical interventions: blood pressure
control, management of anticoagulant-associated brain
hemorrhage and general management principles. Neurol Clin.
2008 Nov;26(4):963-985.
69. Salvetti M, Paini A, Bertacchini F, Aggiusti C, Stassaldi D,
Verzeri L, et al. Therapeutic Approach to Hypertensive
Emergencies: Hemorrhagic Stroke. High Blood Press
Cardiovasc Prev. 2018 Jun;25(2):191-195.
70. Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW.
Inflammation in intracerebral hemorrhage: from
mechanisms to clinical translation. Prog Neurobiol. 2014
Apr;115:25-44.
71. Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA,
Wolfe SQ. Neuroinflammation after Intracerebral
Hemorrhage and Potential Therapeutic Targets. J Stroke.
2020 Jan;22(1):29-46.
72. Chen CJ, Ding D, Ironside N, Buell TJ, Elder LJ, Warren A,
et al. Statins for Neuroprotection in Spontaneous
Intracerebral Hemorrhage. Neurology. 2019 Dec
10;93(24):1056-1066.
73. Bertram M, Bonsanto M, Hacke W, Schwab S. Managing
the Therapeutic Dilemma: Patients with Spontaneous
Intracerebral Hemorrhage and Urgent Need for
Anticoagulation. J Neurol. 2000 Mar;247(3):209-214.
74. Kato Y, Hayashi T, Suzuki K, Maruyama H, Kikkawa Y,
Kurita H, et al. Resumption of Direct Oral Anticoagulants in
Patients with Acute Spontaneous Intracerebral Hemorrhage.
J Stroke Cerebrovasc Dis. 2019 Oct;28(10):104292.
75. Pan X, Li J, Xu L, Deng S, Wang Z. Safety of Prophylactic
Heparin in the Prevention of Venous Thromboembolism
After Spontaneous Intracerebral Hemorrhage: A Meta-
analysis. J Neurol Surg A Cent Eur Neurosurg. 2020
May;81(3):253-260.
76. Murthy SB, Biffi A, Falcone GJ, Sansing LH, Torres Lopez V,
Navi BB, et al. Antiplatelet Therapy After Spontaneous
Intracerebral Hemorrhage and Functional Outcomes. Stroke.
2019 Nov;50(11):3057-3063.
77. De Oliveira M. Surgery for spontaneous intracerebral
hemorrhage. Crit Care. 2020 Feb;24(1):45.
78. Lee BY, Ha S, Lee YH. Association between volume of
surgery for acute hemorrhagic stroke and mortality.
Medicine (Baltimore). 2018 Aug;97(35) e12105.
doi:10.1097/MD.0000000000012105.
79. Torrealba-Acosta G, Carazo-Céspedes K, Chiou SH,
O’Brien AT, Fernández-Morales H. Epidemiology of Stroke in
Costa Rica: A 7-Year Hospital-Based Acute Stroke Registry of
1319 Consecutive Patients. J Stroke Cerebrovasc Dis. 2018
May;27(5):1143–1152.
CORRESPONDENCE
Rosales Bravo, Luis.
luis.rosalesbravo@ucr.ac.cr