Ischemic Stroke

In everyday life, blood clotting is beneficial. When you are bleeding from a wound, blood clots work to slow and
eventually stop the bleeding. In the case of stroke, however, blood clots are dangerous because they can block
arteries and cut off blood flow, a process called ischemia. An ischemic stroke can occur in two ways: embolic and
thrombotic strokes.
Embolic Stroke
In an embolic stroke, a blood clot forms somewhere in the body (usually the heart) and travels through the
bloodstream to your brain. nce in your brain, the clot eventually travels to a blood vessel small enough to block its
passage. !he clot lodges there, blocking the blood vessel and causing a stroke. !he medical word for this type of
blood clot is embolus.
Thrombotic Stroke
In the second type of blood"clot stroke, blood flow is impaired because of a blockage to one or more of the arteries
supplying blood to the brain. !he process leading to this blockage is known as thrombosis. #trokes caused in this
way are called thrombotic strokes. !hat$s because the medical word for a clot that forms on a blood"vessel deposit is
thrombus.
%lood"clot strokes can also happen as the result of unhealthy blood vessels clogged with a buildup of fatty deposits
and cholesterol. &our body regards these buildups as multiple, tiny and repeated in'uries to the blood vessel wall. #o
your body reacts to these in'uries 'ust as it would if you were bleeding from a wound( it responds by forming clots.
!wo types of thrombosis can cause stroke: large vessel thrombosis and small vessel disease (or lacunar infarction.)
Large Vessel Thrombosis
!hrombotic stroke occurs most often in the large arteries, so large vessel thrombosis is the most common and best
understood type of thrombotic stroke. )ost large vessel thrombosis is caused by a combination of long"term
atherosclerosis followed by rapid blood clot formation. !hrombotic stroke patients are also likely to have coronary
artery disease, and heart attack is a fre*uent cause of death in patients who have suffered this type of brain attack.
Small Vessel Disease/Lacunar Infarction
#mall vessel disease, or lacunar infarction, occurs when blood flow is blocked to a very small arterial vessel. !he
term$s origin is from the +atin word lacuna which means hole, and describes the small cavity remaining after the
products of deep infarct have been removed by other cells in the body. +ittle is known about the causes of small
vessel disease, but it is closely linked to hypertension (high blood pressure).
Hemorrhagic Stroke
#trokes caused by the breakage or ,blowout, of a blood vessel in the brain are called hemorrhagic strokes. !he
medical word for this type of breakage is hemorrhage. -emorrhages can be caused by a number of disorders which
affect the blood vessels, including long"standing high blood pressure and cerebral aneurysms. An aneurysm is a
weak or thin spot on a blood vessel wall. !hese weak spots are usually present at birth. Aneurysms develop over a
number of years and usually don$t cause detectable problems until they break. !here are two types of hemorrhagic
stroke: subarachnoid and intracerebral.
In an intracerebral hemorrhage, bleeding occurs from vessels within the brain itself. -ypertension (high blood
pressure) is the primary cause of this type of hemorrhage.
In a subarachnoid hemorrhage, an aneurysm bursts in a large artery on or near the thin, delicate membrane
surrounding the brain. %lood spills into the area around the brain, which is filled with a protective fluid, causing the
brain to be surrounded by blood"contaminated fluid.
.athophysiology
A stroke occurs when the blood flow to an area of the brain is interrupted, resulting in some degree of permanent
neurological damage. !he two ma'or categories of stroke are ischaemic (lack of blood and hence o/ygen to an area
of the brain) and haemorrhagic (bleeding from a burst or leaking blood vessel in the brain) stroke.
.athophysiology of ischaemic stroke
!he common pathway of ischaemic stroke is lack of sufficient blood flow to perfuse cerebral tissue, due to narrowed
or blocked arteries leading to or within the brain.

Ischaemic strokes can be broadly subdivided into thrombotic and embolic strokes.

0arrowing is commonly the result of atherosclerosis 1 the occurrence of fatty pla*ues lining the blood vessels. As the
pla*ues grow in si2e, the blood vessel becomes narrowed and the blood flow to the area beyond is reduced.

3amaged areas of an atherosclerotic pla*ue can cause a blood clot to form, which blocks the blood vessel 1
a thrombotic stroke.

In an embolic stroke, blood clots or debris from elsewhere in the body, typically the heart valves, travel through the
circulatory system and block narrower blood vessels.

%ased on the aetiology of ischaemic stroke, a more accurate sub"classification is generally used:
+arge artery disease 1 atherosclerosis of large vessels, including the internal carotid artery, vertebral artery,
basilar artery, and other ma'or branches of the 4ircle of Willis.
#mall vessel disease 1 changes due to chronic disease, such as diabetes, hypertension, hyperlipidaemia,
and smoking, that lead decreased compliance of the arterial walls and5or narrowing and occlusion of the lumen of
smaller vessels.
6mbolic stroke 1 the most common cause of an embolic stroke is atrial fibrillation.
#troke of determined aetiology 1 such as inherited diseases, metabolic disorders, and coagulopathies.
#troke of undetermined aetiology 1 after e/clusion of all of the above.

In the core area of a stroke, blood flow is so drastically reduced that cells usually cannot recover and subse*uently
undergo cellular death.

!he tissue in the region bordering the infarct core, known as the ischaemic penumbra, is less severely affected. !his
region is rendered functionally silent by reduced blood flow but remains metabolically active. 4ells in this area are
endangered but not yet irreversibly damaged. !hey may undergo apoptosis after several hours or days but if blood
flow and o/ygen delivery is restored shortly after the onset of stroke, they are potentially recoverable (figure 7).
!he ischaemic cascade
After seconds to minutes of cerebral ischaemia, the ischaemic cascade is initiated. !his is a series of biochemical
reactions in the brain and other aerobic tissues, which usually goes on for two to three hours, but can last for days,
even after normal blood flow returns.
!he goal of acute stroke therapy is to normalise perfusion and intervene in the cascade of biochemical dysfunction to
salvage the penumbra as much and as early as possible.
Important steps of the ischaemic cascade
7. Without ade*uate blood supply and thus lack of o/ygen, brain cells lose their ability to produce energy "
particularly adenosine triphosphate (A!.).
8. 4ells in the affected area switch to anaerobic metabolism, which leads to a lesser production of A!. but
releases a by"product called lactic acid.
9. +actic acid is an irritant, which has the potential to destroy cells by disruption of the normal acid"base
balance in the brain.
:. A!."reliant ion transport pumps fail, causing the cell membrane to become depolari2ed( leading to a large
influ/ of ions, including calcium (4a;;), and an efflu/ of potassium.
<. Intracellular calcium levels become too high and trigger the release of the e/citatory amino acid
neurotransmitter glutamate.
=. >lutamate stimulates A).A receptors and 4a;;"permeable 0)3A receptors, which leads to even more
calcium influ/ into cells.
?. 6/cess calcium entry overe/cites cells and activates proteases (en2ymes which digest cell proteins), lipases
(en2ymes which digest cell membranes) and free radicals formed as a result of the ischaemic cascade in a process
called e/citoto/icity.
@. As the cell$s membrane is broken down by phospholipases, it becomes more permeable, and more ions and
harmful chemicals enter the cell.
A. )itochondria break down, releasing to/ins and apoptotic factors into the cell.
7B. 4ells e/perience apoptosis.
77. If the cell dies through necrosis, it releases glutamate and to/ic chemicals into the environment around it.
!o/ins poison nearby neurons, and glutamate can overe/cite them.
78. !he loss of vascular structural integrity results in a breakdown of the protective blood brain barrier and
contributes to cerebral oedema, which can cause secondary progression of the brain in'ury.
.athophysiology of haemorrhagic stroke
-aemorrhagic strokes are due to the rupture of a blood vessels leading to compression of brain tissue from an
e/panding haematoma. !his can distort and in'ure tissue. In addition, the pressure may lead to a loss of blood supply
to affected tissue with resulting infarction, and the blood released by brain haemorrhage appears to have direct to/ic
effects on brain tissue and vasculature.
Intracerebral haemorrhage 1 caused by rupture of a blood vessel and accumulation of blood within the
brain. !his is commonly the result of blood vessel damage from chronic hypertension, vascular malformations, or the
use medications associated with increased bleeding rates, such as anticoagulants, thrombolytics, and antiplatelet
agents.
Subarachnoid haemorrhage is the gradual collection of blood in the subarachnoid space of the brain dura,
typically caused by trauma to the head or rupture of a cerebral aneurysm.
MEASLES
Cact sheet 0D8@=
Cebruary 8B79, W-
Ke facts
)easles is one of the leading causes of death among young children even though a safe and cost"
effective vaccine is available.
In 8B77, there were 7<@ BBB measles deaths globally 1 about :9B deaths every day or 7@ deaths every
hour.
)ore than A<E of measles deaths occur in low"income countries with weak health infrastructures.
)easles vaccination resulted in a ?7E drop in measles deaths between 8BBB and 8B77 worldwide.
In 8B77, about @:E of the world$s children received one dose of measles vaccine by their first birthday
through routine health services 1 up from ?8E in 8BBB.
)easles is a highly contagious, serious disease caused by a virus. In 7A@B, before widespread vaccination,
measles caused an estimated 8.= million deaths each year.
It remains one of the leading causes of death among young children globally, despite the availability of a safe and
effective vaccine. Appro/imately 7<@ BBB people died from measles in 8B77 1 mostly children under the age of
five.
)easles is caused by a virus in the paramy/ovirus family. !he measles virus normally grows in the cells that line
the back of the throat and lungs. )easles is a human disease and is not known to occur in animals.
Accelerated immuni2ation activities have had a ma'or impact on reducing measles deaths. #ince 8BBB, more than
one billion children in high risk countries were vaccinated against the disease through mass vaccination
campaigns F about 88< million of them in 8B77. >lobal measles deaths have decreased by ?7E from an
estimated <:@ BBB to 7<@ BBB.
Signs and sm!toms
!he first sign of measles is usually a high fever, which begins about 7B to 78 days after e/posure to the virus, and
lasts four to seven days. A runny nose, a cough, red and watery eyes, and small white spots inside the cheeks
can develop in the initial stage. After several days, a rash erupts, usually on the face and upper neck. ver about
three days, the rash spreads, eventually reaching the hands and feet. !he rash lasts for five to si/ days, and then
fades. n average, the rash occurs 7: days after e/posure to the virus (within a range of seven to 7@ days).
#evere measles is more likely among poorly nourished young children, especially those with insufficient vitamin
A, or whose immune systems have been weakened by -IG5AI3# or other diseases.
)ost measles"related deaths are caused by complications associated with the disease. 4omplications are more
common in children under the age of five, or adults over the age of 8B. !he most serious complications include
blindness, encephalitis (an infection that causes brain swelling), severe diarrhoea and related dehydration, ear
infections, or severe respiratory infections such as pneumonia. As high as 7BE of measles cases result in death
among populations with high levels of malnutrition and a lack of ade*uate health care. Women infected while
pregnant are also at risk of severe complications and the pregnancy may end in miscarriage or preterm delivery.
.eople who recover from measles are immune for the rest of their lives.
"ho is at risk#
Hnvaccinated young children are at highest risk of measles and its complications, including death. Hnvaccinated
pregnant women are also at risk. Any non"immune person (who has not been vaccinated or was vaccinated but
did not develop immunity) can become infected.
)easles is still common in many developing countries 1 particularly in parts of Africa and Asia. )ore than 8B
million people are affected by measles each year. !he overwhelming ma'ority (more than A<E) of measles
deaths occur in countries with low per capita incomes and weak health infrastructures.
)easles outbreaks can be particularly deadly in countries e/periencing or recovering from a natural disaster or
conflict. 3amage to health infrastructure and health services interrupts routine immuni2ation, and overcrowding in
residential camps greatly increases the risk of infection.
Transmission
!he highly contagious virus is spread by coughing and snee2ing, close personal contact or direct contact with
infected nasal or throat secretions.
!he virus remains active and contagious in the air or on infected surfaces for up to two hours. It can be
transmitted by an infected person from four days prior to the onset of the rash to four days after the rash erupts.
)easles outbreaks can result in epidemics that cause many deaths, especially among young, malnourished
children. In countries where measles has been largely eliminated, cases imported from other countries remain an
important source of infection.
Treatment
0o specific antiviral treatment e/ists for measles virus.
#evere complications from measles can be avoided though supportive care that ensures good nutrition, ade*uate
fluid intake and treatment of dehydration with W-"recommended oral rehydration solution. !his solution
replaces fluids and other essential elements that are lost through diarrhoea or vomiting. Antibiotics should be
prescribed to treat eye and ear infections, and pneumonia.
All children in developing countries diagnosed with measles should receive two doses of vitamin A supplements,
given 8: hours apart. !his treatment restores low vitamin A levels during measles that occur even in well"
nourished children and can help prevent eye damage and blindness. Gitamin A supplements have been shown to
reduce the number of deaths from measles by <BE.
$re%ention
Ioutine measles vaccination for children, combined with mass immuni2ation campaigns in countries with high
case and death rates, are key public health strategies to reduce global measles deaths. !he measles vaccine has
been in use for over :B years. It is safe, effective and ine/pensive. It costs less than one H# dollar to immuni2e a
child against measles.
!he measles vaccine is often incorporated with rubella and5or mumps vaccines in countries where these illnesses
are problems. It is e*ually effective in the single or combined form.
In 8B77, about @:E of the world$s children received one dose of measles vaccine by their first birthday through
routine health services 1 up from ?8E in 8BBB. !wo doses of the vaccine are recommended to ensure immunity
and prevent outbreaks, as about 7<E of vaccinated children fail to develop immunity from the first dose.
"H& res!onse
!he fourth )illennium 3evelopment >oal ()3> :) aims to reduce the under"five mortality rate by two"thirds
between 7AAB and 8B7<. Iecogni2ing the potential of measles vaccination to reduce child mortality, and given
that measles vaccination coverage can be considered a marker of access to child health services, routine
measles vaccination coverage has been selected as an indicator of progress towards achieving )3> :.
verwhelming evidence demonstrates the benefit of providing universal access to measles and rubella"
containing vaccines. >lobally, an estimated <:@ BBB children died of measles in 8BBB. %y 8B77, the global push
to improve vaccine coverage resulted in a ?7E reduction in deaths. #ince 8BBB, with support from the )easles J
Iubella Initiative ()JI Initiative) over 7 billion children have been reached through mass vaccination campaigns
F about 88< million of them in 8B77.
!he )JI Initiative is a collaborative effort of W-, H0I46C, the American Ied 4ross, the Hnited #tates 4enters
for 3isease 4ontrol and .revention, and the Hnited 0ations Coundation to support countries to achieve measles
and rubella control goals.
In April 8B78, the )I Initiative launched a new >lobal )easles and Iubella #trategic .lan which covers the
period 8B78"8B8B. !he .lan includes new global goals for 8B7< and 8B8B:
' the end of ()*+
!o reduce global measles deaths by at least A<E compared with 8BBB levels.
!o achieve regional measles and rubella5congenital rubella syndrome (4I#) elimination goals.
' the end of ()()
!o achieve measles and rubella elimination in at least five W- regions.
!he strategy focuses on the implementation of five core components:
7. achieve and maintain high vaccination coverage with two doses of measles" and rubella"containing
vaccines(
8. monitor the disease using effective surveillance, and evaluate programmatic efforts to ensure progress
and the positive impact of vaccination activities(
9. develop and maintain outbreak preparedness, rapid response to outbreaks and the effective treatment
of cases(
:. communicate and engage to build public confidence and demand for immuni2ation(
<. perform the research and development needed to support cost"effective action and improve vaccination
and diagnostic tools.
Implementation of the #trategic .lan can protect and improve the lives of children and their mothers throughout
the world, rapidly and sustainably. !he .lan provides clear strategies for country immuni2ation managers,
working with domestic and international partners, to achieve the 8B7< and 8B8B measles and rubella control and
elimination goals. It builds on years of e/perience in implementing immuni2ation programmes and incorporates
lessons from accelerated measles control and polio eradication initiatives.
CHARACTERISTIC ILLNESS
After an incubation period of @178 days, measles begins with increasing fever (to 9AD4":B.<D4) and cough, cory2a,
and con'unctivitis K<,=L. #ymptoms intensify over the 81: days before the onset of rash and peak on the first day of
rash K?L. !he rash is usually first noted on the face and neck, appearing as discrete erythematous patches 91@ mm in
diameter. !he lesions increase in number for 8 or 9 days, especially on the trunk and the face, where they fre*uently
become confluent (figure 7). 3iscrete lesions are usually seen on the distal e/tremities, and with careful observation,
small numbers of lesions can be found on the palms of 8<E1<BE of those infected. !he rash lasts for 91? days and
then fades in the same manner as it appeared, sometimes ending with a fine des*uamation that may go unnoticed in
children who are bathed daily. An e/aggerated des*uamation is commonly seen in malnourished children K=, A,7BL.
Cever usually persists for 8 or 9 days after the onset of the rash, and the cough may persist for as many as 7B days.
Moplik$s spots usually appear 7 day before the onset of rash and persist for 8 or 9 days. !hese bluish"white, slightly
raised, 8" to 9"mm"diameter lesions on an erythematous base appear on the buccal mucosa, usually opposite the
first molar, and occasionally on the soft palate, con'unctiva, and vaginal mucosa K77, 78L. Moplik$s spots have been
reported in =BE1?BE of persons with measles but are probably present in most persons who develop measles K79L.
An irregular blotchy enanthem may be present in other areas of the buccal mucosa. .hotophobia from iridocyclitis,
sore throat, headache, abdominal pain, and generali2ed mild lymphadenopathy are also common.
)easles is transmitted by the respiratory route and is highly infectious. Infectivity is greatest in the 9 days before the
onset of rash, and ?<E1ABE of susceptible household contacts develop the disease K7:17=L. !he early prerash
symptoms are similar to those of other common respiratory illnesses, and affected persons often participate in routine
social activities, facilitating transmission. 0umerous outbreaks of disease in highly vaccinated populations occur
when children in the first few days of illness attend sporting events as participants or spectators, especially indoor
events such as basketball and wrestling tournaments K7?187L. utbreaks also occur when ill children are brought to a
doctor$s office or emergency room for evaluation for fever, irritability, or rash
Complications
%y )ayo 4linic #taff
4omplications of measles may include:
Ear infection, ne of the most common complications of measles is a bacterial ear infection.
'ronchitis- larngitis or crou!, )easles may lead to inflammation of your voice bo/ (laryn/) or
inflammation of the inner walls that line the main air passageways of your lungs (bronchial tubes).
$neumonia, .neumonia is a common complication of measles. .eople with compromised immune systems
can develop an especially dangerous variety of pneumonia that is sometimes fatal.
Ence!halitis, About 7 in 7,BBB people with measles develops encephalitis, an inflammation of the brain that
may cause vomiting, convulsions and, rarely, coma or even death. 6ncephalitis can closely follow measles, or it
can occur months later.
$regnanc !roblems, .regnant women need to take special care to avoid measles, because the disease
can cause pregnancy loss, preterm labor or low birth weight.
Lo. !latelet count /thrombocto!enia0, )easles may lead to a decrease in platelets N the type of blood
cells that are essential for blood clotting.