1. Stroke
Neuroscience module.
By Fawz Muzahim
Group :C4/second stage 2017/2018
Medical student/ Baghdad medical college

2. 2
Introduction:
Stroke is sudden death of brain cells result from deprivation of oxygen ,that caused from
blockage of blood flow or rapture of an essential artery of brain[1]or by cerebral thrombosis
that may caused the stroke ,that occurs in varying signs and symptoms from temporary
paralysis and loss of speech to the brain damage and death[2] .
Stroke also called brain attack or CVA (Cerebrovascular Accident)[3],it is one of the most
risky and critical neurological disorder[4] and also it is the third most common cause of
death in development country(after heart disease and cancers)[5].it is cause of death in
people that younger than 45 years ,that cases account 3000 annually ,stroke also is one of 10
causes of death children and that include 5-10% cases of stroke[6].
Stroke is clinical syndrome that’s clinical features develops rapidly through minutes because
of a vascular cause [7].
There are very many causes of stoke more than 150 known causes and also there is unknown
causes [8].The most Common risk factor of stroke divided into 2 groups:
Modifiable fixed
High blood pressure Age
Heart disease(arterial fibrillation, heart attack,
endocarditic)
Gender (more in female)
Diabetic mellitus Race
Hyperlipedaemia hereditary
polycythaemia Previous vascular event (myocardial
infarction, stroke )
Smoking, excess of alcohol High fibrinogen
Social deprivation ,obesity
fig (1), table (1) that shows risk factor of stroke[1].

3. 3
Classification of stroke
Stroke sub typing can help us in describing patients in clinical trial ,divided patients into
groups in an epidemiological study ,phenotyping of patient in a genetic study and classify
patient is benefited in treatment [10].American stroke association published recently an
updated of classification of stroke ,it classes into 2 types ischemic and hemorrhagic [11].
Ischemic stroke:
It is sudden loss of blood flow to an area of brain, it lead to loss of neurological functions ,
it is more common than other types (hemorrhagic stroke)[12].
The main subtypes of ischemic stroke are: Embolic, large artery thromboiotic, Lacunars
stroke, cytogenic stroke and other are less common e.g. arteritis[13].
1-Embolic stroke:
More sever and serious than other sub types of ischemic stroke [14], it involves 20-25% of
ischemic stroke [15].it occur by blockage of one of the arteries to the brain, this is result
from blood clot that has formed elsewhere may be in ascending aorta that is source of
atheromateus emboli [16],frequently emboli from left atrium or the left side heart
valve[15].the major risk factor of embolic stroke is arterial fibrillation , hypertension,
hypercholestremia ,diabetes mellitus , smoking , coronary artery disease[17].
2-thrombotic stroke:
it occurs blood clot that form in one of arteries that supply the brain .the blood clot occurs
by fatty deposit that build up in arteries and lead to atherosclerosis[18],this type of stroke
lead to brain cells in that area to stop function and die very quickly[19], and is most common
cause of ischemic stroke [20].
The risk factors are involve high blood pressure, hyperlipidaemia , smoking, diabetes
,sedentary life style[19].

4. 4
Fig (2) that shows thromboiotic stroke[2]
3-Lacunar stroke:
It is a stroke occurs in deep area of brain e.g.(in thalamus, basal ganglia, pones),occurs by
occlusion in small and deep blood vessels in this area[19].it differ from other types of stroke
that occur in white matter of brain so not affected mental ability but it causes damage the
main conduction fibers that controlling speech,…[5].it very difficult to know and border the
site of lesion [21].
The major risk factors are hypertension and diabetes[19].
4-cytogenic stroke:
Is a cerebral ischemia of unknown origin and the causes also remain until now unknown
[22].it is 40% of ischemia stroke and patient can be seen more than50% of cases of stroke
so it is critical and important [23].

5. 5
A B C
Fig(3) shows different types of ischemia stroke A[cytogenic stroke(3)], B[embolic stroke (2)]
C [LACUNAR stroke (4)].
Hemorrhagic stroke:
It is a Stroke caused by rapture of blood vessel in or on the surface of the brain with bleeding
into surrounding tissue, that caused from aneurysm or an abnormal formed blood
vessels[24].
It is 15% of all stroke.[25],but it responsible for about 40% of all stroke death[26].
Hemorrhagic stroke subtypes are intracerebral hemorrhagic and aneurismal subarachnoid
hemorrhagic [25].
1-Intracerebral hemorrhagic stroke:
Is Also called or known as cerebral bleed is type of intracranial bleed that occurs within the
brain tissue or ventricle [2 7],the causes of ICH include brain trauma ,aneurysm
arteriovenous malformation ,brain tumor[28].
Risk factors of ICH include spontaneous bleeding are high blood pressure, amyloidosis
,alcoholism., low cholesterol and cocaine.ICH occurs more in male and older people[29].

6. 6
2-Subarachnoid hemorrhagic stroke:
Is bleeding into subarachnoid space in the area between the arachnoids membrane and the
pia matter surrounding the brain .it Occurs as result from head injury or aneurysm, risk
factors of SAH are hypertension, smoking and family history.[30],one third of patient will
alive with good recovery, one third will live with a disability and the one third of patient will
be die[31].
Fig (4) subarachnoid stroke [5] Fig (5) intracerebral Stroke [5]

7. 7
History of stroke
Hippocrates who is first recognized stroke over 2,400 years ago. in this time stroke was called
apoplexy, which means "struck down by violence" in Greek. This was because of the fact
that a person developed sudden paralysis and change in well-being[32].
Late on, in the 1600s, the doctor Jacob Wepfer discovered that something disrupted the
blood supply in the brains of people who died from apoplexy. In some of these cases, there
was great bleeding into the brain. In others, the arteries were blocked [33].
in the 1700s, Bonet publishes Sepulchretum sive Anatomical Practica, which becomes a
prominent principle for physicians during the 18th century[34].
In1800s,The earliest known stroke treatments begin to occur, when surgeons start
doing surgery on the carotid arteries. Surgeons begin operating to reduce from cholesterol
build up and remove blockages that could then cause a stroke[35].Reports of successful
closures of injuries to the carotid arteries are documented [36].
In1900sEarly in the 20th century, most of the treatments for stroke patients are limited to
rehabilitation after an acute stroke, and most patients are usually still with permanent and
severe deficits[36].
In the 1950s new techniques and therapies are developed to recognized and modify the
internal processes of cerebrovascular disease[37]. In the 1960s carotid endarterectomy is
used but is used mostly for stroke prevention and there is still no effective treatment after
an acute stroke. In the 1970s aspirin is found to be very effective in stroke prevention. In the
1980s cigarette smoking is found to be a definite risk factor for stroke, and smoking
cessation programs become very important. In the 1990s tissue plasminogen activator starts
to be used for treatment of embolic or thrombotic stroke [36].
Later on in 2000s rapid diagnosis is crucial for direct treatment. Stroke remains the second
most common cause of death worldwide, about 6.7 million patients die in 2012[38].[From
1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12%
in high-income countries, and increased by 12% in low-income and middle-
income countries. In the same time , mortality rates presented a significant decrease in all
countries[39].

8. 8
sEpidemiology of stroke
Stroke was the second most cause of death in 2011, accounting for 6.2 million deaths (~11%
of the total)[38], Approximately 17 million people had a stroke in 2010 and 33 million people
have previously had a stroke and were still survive [39].
Between 1990 and 2010 the number of strokes decreased by approximately 10% in the
developed world and increased by 10% in the developing world,Overall, two-thirds of
strokes happened in those over 65 years old.[14] South Asians are at particularly high risk
of stroke, it is 40% of global stroke deaths[38]. In the United States stroke is a leading cause
of disability, and recently declined from the third leading to the fourth leading cause of
death[40].Geographic disparities in stroke incidence have been observed, including the
existence of a "stroke belt" in the south eastern United States, but causes of these disparities
have not been explained[39].
The risk of stroke increases from 30 years of age, and the cause of stroke varies by age[41].
one of the most significant stroke risk factors is advanced age or elder people, 95% of strokes
happen in people age 45 and older, and two-thirds of strokes happen in these over the age of
65[22].
stroke can happen at any age, including in childhood,Family members may have a genetic
tendency for stroke or share a lifestyle lead to stroke. Higher levels of Von Will brand
factor are more common with people who have had ischemic stroke for the first
time.[39] The results of this found that the only significant genetic factor was the
person's blood type. Having had a stroke in the past greatly increases one's risk of future
strokes , Men are 25% more likely to suffer from strokes than women [25]. Yet 60% of
deaths from stroke happen in women[42].
Fig (6); subtypes of stroke and its incidence[6]

9. 9
clinical features of patient with stroke
The clinical presentation of stroke depends on which arterial territory is included and the
size of the lesion, both of which will have a sharing on management, such as appropriate for
carotid endarterectomy. The neurological deficit can be recognized and identified from the
patient’s history and, if the deficit is persistent, from the neurological examination[9].clinical
feature different from person to other depend on the the cause of stroke and type of
strok[43],most common signs and symptoms are:
1-Hemiparesis, monoparesis, or (rarely) quadriparesis.
2-Hemisensory deficits.
3-Monocular or binocular visual loss.
4-Visual field deficits.
5-Diplopia.
6-Dysarthria.
7-Facial droop.
8-Ataxia.
9-Vertigo (rarely in isolation).
10-Aphasia.
11-Sudden decrease in the level of consciousness.[44][43].
clinical features of The ischemic strokes subtypes:
1-embolic stroke : sudden onest of signs and symptoms with deficit maximal at onset[43].
2_thrombosis stroke:clinical features of it involve essentially of headache, focal neurologic
deficit ,epileptic, seizures and impairment of consciousness, in different combination and
degree of severity ,the onest of headache usually gradual but in up to 15 of patients it is
sudden[45].
3-Lacunar stroke: clinical features of it are five which well recognized: pure motor hemi
paresis, pure sensory stroke, sensorimotor stroke, dysarthria—clumsy hand syndrome[46].

10. 10
Clinical features of hemorrhagic stroke:
In subarachnoid hemorrhagic stroke,clinical feature is sudden onest of sever diffuse
headache that peaks within minutes and usually lasts 1_2 weeks,in generalpractice the
headache is only symptoms of one third of patient of subarachnoid hemorrhagic stroke .[45]
Other sign associated vomiting,headache and vomiting occur in hemorrhagic stroke more
than ischemic stroke because of increased in intracranial pressure[43].
Causes of stroke
Stroke may be caused by a blocked artery (ischemic stroke) or the leaking or bursting of a
blood vessel (hemorrhagic stroke) ,or (Transient ischemic attack )also known as a mini_
stroke occurs when a clot or debris blocks blood flow to part of brain. is a brief period of
symptoms , which often last less than five minutes because the blockage is temporary[18].
Type of stroke causes
Intracerebral hemorrhage stroke Complex small vessels disease with distribution
of vessel wall,amyloid angiopathy,impaired
blood clotting ,vascular anomaly ,substance
misuse .
Subarachnoid hemorrhage stroke Vertebral dissection,saccular anyrusym
Ischemic stroke Cardic source[arrhythmias,valve
disorder,dilated cardiomyopathy,recent
myocardial infraction paradoxical
emboli],small vessels occlusive disease
[hypertension,isolated central nervous system
a niglitis,systemic lupus erythematosus],large
vessel disorder[atheroscelrosis,or dissection in
carotid or vertebrobasilar
system],hematological disorder[polycithemia,
thrombocytosis, sever leukocytosis,protein c
deficiency , …]
Fig(7) in this table shows the diseases and disorder that causes the stroke[1]

11. 11
Pathogenesis of stroke
Ischemic stroke:
is often occurred due to a lack of blood flow to all or part of the brain ,resulting in
deprivation of neurons of vital glucose and oxygen, this deprivation if it sever and prolonged
,result in interruption of normal cellular processes and eventual cell death with breakdown
of the neuronal cell membrane[47],also it resulting in Atherosclerosis that could disrupt the
blood supply by narrowing the lumen of blood vessels that caused reduction of blood flow,
by causing the formation of blood clots within the vessel, or by releasing showers of
small emboli through the disintegration of atherosclerotic plaques[48].
since the blood vessels of brain blocked , the brain becomes decreased in energy, and thus it
resorts into using anaerobic metabolism within the region of brain tissue affected by
ischemia Anaerobic metabolism produces low adenosine triphosphate (ATP) but releases a
by-product called lactic acid[47]. Lactic acid is an irritant which could potentially destroy
cells since it is an acid and disrupts the normal acid-base balance in the brain. The ischemia
area is known as the "ischemic penumbra”[49].
A major cause of neuronal injury is the release of the excitatory neurotransmitter glutamate.
The concentration of glutamate outside the cells of the nervous system is normally kept in
low concentration by so-called uptake carriers, which are powered by the concentration
gradients of ions (mainly Na+) across the cell membrane[9]. However, stroke cuts off the
supply of oxygen and glucose which supported the ion pumps maintaining these
gradients[46]. As a result, the transmembrane ion gradients run down, and glutamate
transporters reverse their direction, releasing glutamate into the extracellular space[49].
Glutamate acts on receptors in nerve cells (especially NMDA receptors), producing an influx
of calcium which activates enzymes that digest the cells' proteins, lipids, and nuclear
material. Calcium influx can also lead to the failure of mitochondria, which can lead further
toward energy depletion and may trigger cell death due to programmed cell death[50]..
Ischemia also induces production of oxygen free radicals and other reactive oxygen species.
These react with and damage a number of cellular and extracellular elements[9]. In fact,
many antioxidant neuroprotectants such as uric acid and NXY-059 act at the level of the
endothelium and not in the brain per se. Free radicals also directly initiate elements of the
programmed cell death cascade by means of redox signaling[51].
Hemorrhagic stroke:
Hemorrhagic strokes are classified depended on their underlying pathology and etiology
into intracerebral and subarachnoid hemorrhagic stroke [52],this stroke caused by

12. 12
hypertension,anticoagulant,bleeding disorder, cerebral amyloid angiopathy ,ruptured
arterial aneurysm ,arteriovenous malformation[53].
Intracerebral hemorrhagic stroke:
Is an fatal type that caused 30,000 death cases annually in united states [54]. The bleeding
occurs into brain parenchyma happened in this type of stroke, the mechanisms of
intracerebral hemorrhagic stroke included leakage from the small intracerebral arteries
damaged that caused by chronic hypertension, other mechanism involved bleeding
diatheses, iatrogenic anticoagulation and cerebral amyloidosis[55]. The common locations of
cerebral arteries aneurysms are close to the anterior communication and anterior cerebral
arteries, close to junctions close to middle cerebral artery and at the junction between basilar
and posterior cerebral artery[56],the most common sites of intracerebral hemorrhagic
stroke are thalamus,putamen ,cerebellum and brainstem[55] .
Intracerebral hemorrhagic stroke involves 3 phases: 1) initial hemorrhage.2) hematoma
expansion. 3)peri-hematoma edema[57].
Initial hemorrhage is result from rupture of cerebral artries that caused by chronic
hypertension and other risk factor of ICH,hematoma expansion happened through hours
after initial symptom onset, includes an increasing in intracranial pressure that affect on the
integrity of the local tissue and blood brain barrier and also affected on obstructed venous
outflow that induces the release of tissue thromboplastin[58].hematoma expansion is
associated with hyperglycemia, hypertension and anticoagulation [59].the initial size of
hemorrhagic and the rate of hematoma expansion are important in prognosis, the hematoma
that its size>30 ml is lead to increased mortality[60].cerebral edema forms around the
hematoma ,secondary to inflammation and damaged of blood brain barrier, and it develops
over days[59].
Subarachnoid hemorrhagic stroke: Is life threatening type of stroke result from
bleeding occurs in the two inner most protective covering layers of brain ( subarachnoid
space between the pia and arachnoid) due to aneurysms or arterial venous malformation,
aneurysms are specific to intracranial arteries because it doesn’t have an external elastic
lamina and involved very thin adventitia [61].after hemorrhage the subarachnoid space is
filled by erythrocytes in cerebrospinal fluid ,these erythrocytes follow many pathways, some
will shared with a clot that forms in bleeding site ,and other will be enclosed in arachnoids
villi and cleared from cerebrospinal fluid into blood vessels within a day and the majority
cleared within a week, and other erythrocytes removed by phagocytosis[62].

13. 13
Treatment of stroke
Ischemic stroke
the only emergency approved treatment for ischemic strokes is tissue plasminogen activator
also known as IV rtPA,given through IV in the arm, tPA act by dissolving the clot and allow
blood flow into the part of brain that deprived from blood flow and it give also chances to
recovering from stroke[63]. The drugs that also used to treat the patient who have a stroke
are involve: platelet aggregation inhibitors ( e.g. clopidogrel),thrombolytic (e.g. alteplase
systemic),calcium channel blocking (e.g. nimodipine ),ACEI,betabloker ( e.g. labetalol),
vasodilator ,vitamin k antagonist, aspirin that reduces the overall risk of recurrence by 13%
[64] .
another treatment option is an endovascular procedure that known as thrombectomy ,by
this procedure the large blood clot can removed by using a catheter through an artery that
is blocked in brain[63].
Hemorrhagic stroke :
the treatment of patient with acute intracerebral hemorrhage depend on the cause and
severity of bleeding ,the medication that used in treatment of acute stroke
involve;anticonvulsant (for prevention of the seizure recurrence),antihypertensive agents
(for reduction blood pressure) and osmotic diurites for decreasing the intracranial pressure
in subarachnoid space[65].
Surgical treatments are present in treatment of hemorrhagic stroke to stop bleeding ,by
metal clip may be placed surgically at the base of the aneurysm to secure it [63].
In subarachnoid hemorrhage, early treatment for underlying cerebral aneurysms may
reduce the risk of further hemorrhages. Depending on the site of the aneurysm this may be
by surgery that involves opening the skull or endovascular (through the blood vessels)[66].

14. 14
Diagnosis of stroke:
Mainly by CT scan and MRI and other testing depend on type of stroke[65].See fig(8).
.fig(8)Table that show investigation of stroke[1].
Prevention of stroke
primary prevention include using aspirin for cardiovascular prophylaxis was taking
from2002 ,Statins reduce the risk of ischemic stroke in patients at high risk of atherosclerosis
and are well tolerated[65].
Secondary prevention refers to the treatment of individuals who have already had a stroke
or transient ischemic by using clopidogrel and aspirin, The comparative benefits of
clopidogrel and aspirin plus ER-DP in secondary stroke prevention are under evaluation in
the ongoing Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study,
which has enrolled >20 000 patients with a recent history of ischemic stroke randomized to
either the combination of ER-DP plus aspirin or clopidogrel monotherapy. With results
expected in 2008[67].
Tertiary prevention :goes beyond secondary prevention measures to address the care of
persons who have already suffered a first stroke. Tertiary measures are aimed at the
prevention of a second or third stroke and the minimalization of disability through patient
Diagnostics question Investigation
Is it a vascular lesion? CT scan/MRI
Is it ischemic or hemorrhagic ? CT scan/MRI
Is it subarachnoid hemorrhagic? CTscan/ lumber puncture.
Is there any cardiac source of embolism ? Electrocardiogram
Echocardiogram
What are the risk factors? Full blood count.
Cholesterol.
Blood glucose.
Is there unusual cause? ERS.
SERUM protein electrophoresis
Clotting / thrombophillia screen

15. 15
rehabilitation, in order torestablish partial or complete independence and improve quality
of life[ 22].
Fig( 9)Strategies for secondary prevention of stroke.[1]

16. 16
Summary:
Stroke is sudden death of brain cells due to lack of oxygen, caused by blockage of blood flow
or rapture of an artery to the brain or cerebral thrombosis may cause the stroke which can
occur in varying degree of severity from temporary paralysis and slurred speech to
permanent brain damage and death. Stroke is the third most common cause of death (after
heart attack and cancers) in developing countries. Stroke is clinical Syndrome characterized
by rapidly developing (usually over minutes)symptoms or signs of focal neurological
dysfunction due to a vascular cause. Very recently the American stroke association published
an updated for classification of stroke it classes into 2 types ischemic and hemorrhagic.
Ischemic stroke It is characterised by sudden loss of blood circulation to an area of brain
resulting in a corresponding loss of neurologic function ,it is more common than
hemorrhagic stroke. The main subtypes of ischemic stroke are: Embolic ,large artery
thromboiotic ,small vessel (lacunar ) stroke , cytogenic stroke.
Hemorrhagic stroke Stroke caused by rapture of blood vessel in or on the surface of the brain
with bleeding into surrounding tissue ,occur from aneurysm or an abnormal formed blood
vessels. Hemorrhagic stroke subtypes are intracerebral hemorrhagic and aneurysmal
subarachnoid hemorrhagic.
Hippocrates, the father of medicine, first recognized stroke over 2,400 years ago. At this time
stroke was called apoplexy, which means "struck down by violence" in Greek. This was due
to the fact that a person developed sudden paralysis and change in well-being.
Stroke Having had in the past greatly increases one's risk of future strokes ,Men are 25%
more likely to suffer strokes than women . yet 60% of deaths from stroke occur in women.
The clinical presentation of stroke depends upon which arterial territory is involved and the
size of the lesion, both of which will have a bearing on management.
Ischemic stroke: is often due to a lack of blood flow to all or part of the brain ,resulting in
deprivation of neurons of vital glucose and oxygen, this deprivation if sever and prolonged
,result in interruption of normal cellular processes and eventual cell death with breakdown
of the neuronal cell membrane.
Hemorrhagic stroke :this stroke caused by hypertension,anticoagulant,bleeding disorder,
cerebral amyloid angiopathy ,ruptured arterial aneurysm ,arteriovenous malformation.
The management of stroke depended on the type of it ,mainly diagnosis by CT Scan and
MRI,treatment by medication or surgically depended on the type of stroke .
The prevention involve primary ,secondary and tertiary , generally it summarized by
reduction of occurring the risk factor of stroke.

17. 17
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