LEC: 5 STROKE Dr: Zainab T.

Jaddoa

ETIOLOGY
Strokes can either be ischemic (87% of all strokes) or hemorrhagic (13% of all strokes). Ischemic
stroke, which may be thrombotic or embolic, is the abrupt development of a focal neurological
deficit that occurs due to inadequate blood supply to an area of the brain.

A thrombotic occlusion occurs when a thrombus forms inside an artery in the brain. An embolic
stroke typically occurs when a piece of thrombus, originating either inside or outside of the
cerebral vessels, breaks loose and is carried to the site of occlusion in the cerebral vessels. An
extracerebral source of emboli is often the heart, leading to cardioembolic stroke.

Hemorrhagic stroke is a result of bleeding into the brain and other spaces within the central
nervous system (CNS) and includes subarachnoid hemorrhage (SAH), intracerebral hemorrhage
(ICH), and subdural hematomas.

SAH results from sudden bleeding into the space between the inner and middle layers of the
meninges, most often due to trauma or rupture of a cerebral aneurysm or arteriovenous
malformation (AVM). ICH is bleeding directly into the brain parenchyma, often as a result of
chronic uncontrolled hypertension. Subdural hematomas result from bleeding under the dura
that covers the brain and most often occur as a result of head trauma.

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Cerebral Ischemic Events
There are two main classifications of cerebral ischemic events: transient ischemic attack (TIA)
and ischemic stroke (cerebral infarction).

Transient ischemic attacks (TIAs) are focal ischemic neurologic deficits lasting less than 24
hours and usually less than 30 minutes (no deficit remains after the attack) .

Ischemic stroke is similar to TIA; however, tissue injury and infarction are present, and in many
patients, residual deficits remain after the event.

TIAs are a risk factor for acute ischemic stroke, preceding acute ischemic stroke in
approximately 15% of cases; therefore, preventive measures are the same for both TIA and
ischemic stroke

Risk Factors

Nonmodifiable Risk Factors

••Age (> 55 years) ••Gender (males more than females) ••Race and ethnicity (American
Indian/Alaska Natives, African American, Asian/Pacific Islander, Hispanic) ••Genetic
predisposition ••Low birth weight
Well-Documented and Modifiable Risk Factors
••Hypertension ••Cardiac disease ••Atrial fibrillation (most important and treatable cardiac cause
of stroke) ••Valvular heart disease ••Left atrial enlargement ••Structural abnormalities such as
atrial septal aneurysm ••Acute myocardial infarction ••Transient ischemic attacks or prior stroke
(major independent risk factor) ••Diabetes (independent risk factor) ••Dyslipidemia
••Asymptomatic carotid stenosi
••Oral contraceptive use (with estrogen content > 50 mcg) ••Postmenopausal hormone therapy
••Sickle cell disease
••Lifestyle factors ••Cigarette smoking ••Excessive alcohol use ••Physical inactivity ••Obesity
••Diet
••Cocaine and intravenous drug use ••Low socioeconomic status
Less Well-Documented or Potentially Modifiable Risk Factors
••Increased hematocrit ••Metabolic syndrome ••Hyperhomocysteinemia ••Migraine (risk not
clear)
••Sleep disordered breathing (ie, sleep apnea)

DESIRED TREATMENT OUTCOMES

The short-term treatment goals for acute ischemic stroke include reducing secondary brain
damage by reestablishing and maintaining adequate perfusion to marginally ischemic areas of the
brain& protecting these areas from the effects of ischemia (ie, neuroprotection).
Long-term treatment goals for acute ischemic stroke include prevention of a recurrent stroke
through reduction and modification of risk factors and by use of appropriate treatments.

Short-term treatment goals for hemorrhagic stroke include rapid neuro intensive care to
maintain adequate oxygenation, breathing, and circulation. Management of increased ICP and
blood pressure (BP) are important in the acute setting.

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 Long term management includes prevention of complications and of a recurrent bleed and
delayed cerebral ischemia.

Prevention of long-term disability and death related to stroke are important regardless of stroke
type.

Clinical presentation
General
•• Patient may not be able to reliably report history owing to cognitive or language deficits. A
reliable history may have to come from a family member or another witness.
Symptoms
•• The patient may complain of weakness on one side of the body, inability to speak, loss of
vision, vertigo, headache, or falling.
Signs
•• Hemiparesis ‫شلل نصفي‬or monoparesis ‫ شلل لطرف واحد‬occur commonly
•• Patients with vertigo and double vision
•• Aphasia ‫صعوبه بلع‬
•• Patients may also suffer from dysarthria,‫ عسر اللفظ‬visual field defects, and altered levels of
consciousness.

Signs and Symptoms of Hemorrhagic Stroke

•• A sudden severe headache, nausea, vomiting, and photophobia may be the first signs and
symptoms. Patients may complain the headache is “the worst headache of my life,” especially if
the cause is a SAH.
•• Neck pain and nuchal rigidity may also be experienced at the time of the hemorrhage.
** It is important to note that a diagnosis of type of stroke cannot be made solely on signs and
symptoms because overlap occurs between types of stroke.

Diagnostic Tests
•• Computed tomography (CT) scan of the head will reveal an area of hyperintensity (white)
identifying that ahemorrhage has occurred. The CT scan will either be normal or hypointense
(dark) in an area where an infarction has occurred. It may take 24 hours (and rarely longer) to
reveal the area of infarction on a CT scan.
•• Magnetic resonance imaging (MRI) of the head will reveal areas of ischemia earlier and
with better resolution than a CT scan.
•• Carotid Doppler studies will determine whether the patient has a high degree of stenosis in
the carotid arteries supplying blood to the brain (extracranial disease).
•• Electrocardiogram (ECG) will determine whether the patient has AF, a major risk factor for
cardioembolic stroke.
•• Transthoracic echocardiogram will identify whether there are heart valve abnormalities or
problems with wall motion of the heart resulting in emboli to the brain

Desired Outcomes
The goals of treatment of acute stroke are to:
(a) Reduce the ongoing neurologic injury and decrease mortality and long-term disability,
(b) Prevent complications secondary to immobility and neurologic dysfunction.

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(c) Prevent stroke recurrence (through reduction and modification of risk factors and by use of
appropriate treatments)

TREATMENT OF ACUTE ISCHEMIC STROKE

The time the patient was last without symptoms is used as the time of stroke onset. Because
patients typically do not experience pain, determining the onset time can be difficult. It is also
important to document risk factors and previous functional status to assess current disability due
to stroke

Supportive Measures
Acute complications of ischemic stroke include cerebral edema, increased ICP, seizures, and
hemorrhagic conversion. In the acute setting, supportive interventions and treatments to prevent
acute complications should be initiated. Cardiac monitoring, most commonly with a Holter
monitor, should be continued for the first 24 hours to screen for atrial fibrillation (AF) and other
cardiac diseases.

❖ Tissue oxygenation should be maintained acutely. Measure the oxygen saturation using
pulse oximetry and supplement the patient with oxygen if necessary. Oxygen saturation
should be maintained at 94% or greater.
❖ Volume status and electrolytes should be corrected. If required,
❖ blood glucose should be corrected because both hyperglycemia and hypoglycemia may
worsen brain ischemia. When blood glucose less than 60 mg/dL (3.3 mmol/L) is present,
bolus with 25 mL of 50% dextrose immediately. Patients with elevated blood glucose
poststroke have been documented to have worse outcomes; therefore, lowering the blood
glucose to between 140 and 180 mg/dL (7.8–10.0 mmol/L) with subcutaneous insulin is a
reasonable approach.
❖ If the patient is febrile, treat with acetaminophen because fever is associated with brain
ischemia and increased morbidity and mortality after stroke. Alternatively, cooling
devices can be used.
❖ Low-dose unfractionated heparin (UFH) or low-dose low molecular weight heparin
(LMWH) administered subcutaneously significantly decrease the risk of developing
venous thromboembolism (VTE) poststroke. UFH 5000 units subcutaneously every 8 to
12 hours or low-dose LMWH should be given for VTE prophylaxis in patients who are
not candidates for intravenous (IV) alteplase. In patients receiving IV alteplase, the
administration of subcutaneous UFH or LMWH should be delayed until 24 hours after
the administration of alteplase to avoid bleeding complications.
❖ up to 75% of patients have an elevated BP in the first 24 to 48 hours. BP should be
optimized;
however, hypertension should generally not be treated in the acute period (12–24 hours) because
it may cause decreased blood flow in ischemic areas, potentially increasing the infarction size.
The cautious use of antihypertensive medications may be necessary in patients who are
otherwise candidates for fibrinolytic therapy, including those with severely elevated BP (systolic
BP greater than 220 mm Hg or diastolic BP [DBP] greater than 120 mm Hg), and those with
other medical disorders requiringimmediate lowering of BP. and provide recommendations on
BP management in those eligible and not eligible for alteplase. In those not eligible for alteplase,

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when BP is lowered, aim for a 15% reduction in systolic BP and diastolic BP in the first 24 hours
after stroke onset. BP should be checked three times with each reading taken 5 minutes apart.

1. Heparin
a. not recommended for stroke treatment at therapeutic doses; increases risk of hemorrhagic
transformation; heparin is often used for deep venous thrombosis prevention at a dose of 10,000–
15,000 units/day administered subcutaneously
b. Avoid in hemorrhagic stroke
2. Tissue plasminogen activator (Alteplase)
a. Within 4½ hours of symptom onset
b. 90-day outcomes significantly improve (decreased disability).
c. Intracerebral hemorrhage increases but mortality does not.
d. Dose 0.9 mg/kg intravenously (maximum is 90 mg), with 10% as a bolus and the remainder
over 1 hour. The bolus should be administered within 60 minutes of hospital arrival.
e. Antiplatelet agents should be held for 24 hours after tissue plasminogen activator
administration.
f. Exclusion criteria
i. Intracranial bleeding (or history) or subarachnoid bleeding
ii. Other active internal bleeding
iii. Intracranial/spinal surgery, head trauma, stroke within 3 months
iv. Major surgery or serious trauma within 2 weeks, if risk of bleeding outweighs the anticipated
benefits of reduced stroke-related neurologic deficits
v. GI hemorrhage within 3 weeks or structural GI malignancy
vi. Blood pressure greater than 185/110 mm Hg. If medications are administered to lower blood
pressure, blood pressure should be stabilized before beginning treatment and maintained
below 180/105 mm Hg for at least the first 24 hours after treatment.
vii. Glucose less than 50 mg/dL or greater than 400 mg/dL, unless subsequently normalized
viii. Arterial puncture at a noncompressible site within 1 week
ix. Intracranial intra-axial neoplasm, arteriovenous malformation, or giant unruptured and
unsecured aneurysm

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x. INR greater than 1.7, activated PTT greater than 40 seconds, PT greater than 15 seconds, Plt
less than 100,000 cells/m3, patients who have received a dose of low-molecular-weight heparin
within the previous 24 hours, or patients who have taken direct thrombin inhibitors or direct
factor Xa inhibitors in the previous 48 hours
xi. Infective endocarditis
xii. Pregnancy, if the anticipated benefits of treating moderate to severe stroke do not outweigh
the anticipated risks of uterine bleeding
xiii. Individuals presenting in the 3- to 4½-hour window may benefit even if they are older than
80, take warfarin, have a history of diabetes with previous stroke, or have severe stroke
symptoms
3. In patients with minor strokes or transient ischemic attack (TIA), DAPT with aspirin and
clopidogrel should be initiated immediately and continued for 21 days.
4. A clot retriever within 24 hours may be useful in selected patients with or without prior tissue
plasminogen activator.

PREVENTION OF ACUTE ISCHEMIC STROKE

Primary Prevention
1. Reduction in risk factors (e.g., control of hypertension, smoking cessation, control of diabetes,
cholesterol reduction). Control of hypertension produces the greatest benefit in primary
prevention of stroke.

2. Patient education: Patients should be educated about stroke warning signs and instructed to
seek emergency care if they have any of them. Warning signs: Sudden numbness or weakness of
the face, arm, or leg, especially on one side of the body; sudden confusion; trouble speaking or
understanding; sudden trouble seeing in one or both eyes; sudden trouble walking; dizziness, loss
of balance or coordination; sudden, severe headache with no known cause

3. Treatment of atrial fibrillation: Up to 70% of cases are inappropriately treated. NVAF

increases the risk of stroke by 5-fold compared with patients without AF. AF is responsible for
15% of all strokes.

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a. Dabigatran (Pradaxa): When oral anticoagulation is recommended and the patient’s bleeding
risk is high, current guidelines suggest dabigatran 150 mg twice daily over warfarin (target INR
of 2.5). Dabigatran had similar rates of hemorrhage, but intracranial hemorrhage was less likely
with dabigatran and GI hemorrhage was more likely.
b. Rivaroxaban was noninferior to warfarin therapy and had a similar risk of major bleeding.
Rivaroxaban had a higher risk of GI bleeding, but a lower risk of intracranial hemorrhage and
fatal bleeding, compared with warfarin therapy.
c. Apixaban is more effective than warfarin, with a lower risk of stroke and lower risk of
bleeding and mortality.
d. Edoxaban is as effective as warfarin, with a lower risk of bleeding.
e. Warfarin is probably more effective than clopidogrel plus aspirin, but intracranial
bleeding is more common.

Secondary Prevention
1. Reduction in all modifiable risk factors
a. Hypertension: Goal less than 130/less than 80 mm Hg.
b. Hyperlipidemia: High-intensity statin therapy should be initiated or continued as first-line
therapy in women and men younger than 75 who have had stroke or TIA. It is now
recommended that patients experiencing ischemic stroke of presumed atherosclerotic origin, with
low-density lipoprotein (LDL) greater than 100 mg/dL, be treated with high-intensity statin
therapy for secondary stroke prevention

2. Carotid endarterectomy if 70%–99% stenosis. For 50%–69% stenosis, the carotid

endarterectomy recommendation depends on age, sex, and comorbidities; use aspirin 50–100
mg/day and statin therapy before and after the procedure.

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3. Carotid angioplasty and stenting may be an alternative to carotid endarterectomy in some
patients, particularly younger patients.

4. Antiplatelet therapy: DAPT with aspirin and clopidogrel should be initiated within 24 hours of
a minor stroke or TIA and continued for 21 days. After a major stroke (e.g., intracranial
atherosclerosis, severe stenosis), DAPT with aspirin and clopidogrel should be initiated and
continued for 90 days. After these time intervals, therapy should be transitioned to single
antiplatelet therapy and continued indefinitely.

The American Stroke Association suggests that aspirin, aspirin/extended-release dipyridamole,

and clopidogrel are all options for ongoing prophylaxis.
a. Aspirin
i. Dose: 50–100 mg/day
ii. If the patient has an additional stroke while taking aspirin, no evidence suggests increasing the
aspirin dose will provide additional benefit.
b. Aspirin/dipyridamole (Aggrenox)
i. Capsule contains dipyridamole extended-release pellets (200 mg) and aspirin tablet (25 mg).
ii. Dose: 1 capsule orally twice daily
iii. Most common adverse effects: Headache, nausea, and dyspepsia; can increase liver enzymes

c. Clopidogrel (Plavix)
i. Inhibits adenosine diphosphate–induced platelet aggregation
ii. Dose: 75 mg/day orally
iii. Very low incidence of neutropenia (0.04% severe)
iv. Rarely, thrombotic thrombocytopenic purpura has been reported.
v. Partly metabolized by CYP2C19; interactions may occur with inhibitors of CYP2C19, notably
proton pump inhibitors, or with genetic polymorphisms of this enzyme.

d. Cilostazol (Pletal)
i. Inhibits cyclic adenosine monophosphate phosphodiesterase type 3–induced platelet
aggregation
ii. Dose: 100 mg orally twice daily on an empty stomach
iii. Metabolized extensively by CYP3A4 and CYP2C19
iv. Adverse effects: Headache, palpitation, diarrhea, and dizziness; rarely, thrombocytopenia or
agranulocytosis

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v. Contraindicated in patients with congestive heart failure
vi. Monitoring: CBC with differential every 2 weeks for 3 months; periodically thereafter. Thus,
used infrequently

5. Anticoagulation: Warfarin (or direct oral anticoagulants(dabigatran, rivaroxaban, apixaban,

edoxaban)
a. Prevention of second ischemic event, if patient has atrial fibrillation (warfarin or direct oral
anticoagulants), rheumatic mitral valve disease (warfarin), mechanical prosthetic heart valves
(warfarin), bioprosthetic heart valves (warfarin), or left ventricular mural thrombus formation
(warfarin)
b. Target INR: 2–3 for nonvalvular atrial fibrillation; 2.5–3.5 for mechanical prosthetic heart
valves

TREATMENT OF ACUTE HEMORRHAGIC STROKE

Supportive Measures
Acute hemorrhagic stroke is considered to be a medical emergency due to intracerebral
hemorrhage (ICH), subarachnoid hemorrhage (SAH), or subdural hematoma. Initially, patients
experiencing a hemorrhagic stroke should be transported to a neuro intensive care unit. There is
no proven treatment for ICH. Management is based on neurointensive care treatment and
prevention of complications. Treatment should be provided to manage the needs of the
critically ill patient including management
❖ of increased ICP, seizures, infections, and prevention of rebleeding and delayed cerebral
ischemia.
❖ In those with severely depressed consciousness, rapid endotracheal intubation and
mechanical ventilation may be necessary.

❖ BP is often elevated after hemorrhagic stroke; appropriate management is important to

prevent rebleeding and expansion of the hematoma. In patients presenting with SBP
greater than 220 mm Hg, BP lowering using continuous IV infusion is recommended.

When SBP is between 150 and 220 mm Hg, lowering of the SBP to less than 140 mm Hg
does not improve outcomes and may cause harm compared to a less aggressive BP

BP can be controlled with IV boluses of labetalol 10 to 80 mg every 10 minutes up to a

maximum of 300 mg or with IV infusions of labetalol (0.5–2 mg/min) or nicardipine (5–
15 mg/hour).
❖ Deep vein thrombosis prophylaxis with intermittent compression stockings should be
implemented early after admission. In those patients with SAH, once the aneurysm has
been treated, heparin may be instituted. In ICH patients with lack of mobility after 1 to 4
days, heparin or LMWH may be started.

Nonpharmacologic Therapy

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1-Patients with hemorrhagic stroke are evaluated for surgical treatment of SAH and ICH. In
SAH, either clipping of the aneurysm or coil embolization is recommended within 72 hours after
the initial event to prevent rebleeding .

2-Current guidelines note that surgical treatment of ICH is uncertain and is not recommended
except in specific patient situations

Pharmacologic Therapy
»» Calcium Antagonists Oral nimodipine is recommended in SAH to prevent delayed cerebral
ischemia. It is recommended to begin oral nimodipine promptly after the initial event, but no
later than 96 hours following SAH. Delayed cerebral ischemia occurs 4 to 14 days after the
initial aneurysm rupture and is a common cause of neurological deficits and death. oral
nimodipine 60 mg every 4 hours for 21 days following aneurysmal SAH reduced the risk of a
poor outcome and delayed cerebral ischemia.

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