Transient Ischemic Attack

A transient ischemic attack (TIA) describes the clinical

condition in which a patient experiences a temporary
focal neurologic deficit such as slurred speech,
aphasia, weakness or paralysis of a limb, or blindness.
These symptoms appear rapidly and are temporary,
lasting
<24 hours (usually only 2–15 minutes).
TIAs frequently result from small clots breaking away from
larger, distant blood clots. These emboli are then
dissolved by the fibrinolytic system, allowing re-
establishment of blood flow and return of neurologic 2
 Stroke
Stroke: Abrupt-onset focal neurologic deficit that lasts
for 24 hours and is of presumed vascular origin. It could
be either:

Ischemic = Clot (makes up approximately 88% of all

strokes)

Hemorrhagic = Bleed, makes up approximately 12 % of

cases

3
Ischemic Versus Hemorrhagic
 Cerebrovascular Accident (stroke)

• 2nd leading cause of death worldwide

• 3rd leading cause of death in the U.S.
- After cardiovascular diseases & all cancers
combined)
• Leading cause of adult disability in the U.S.
• Costly (Up to $70 billion/year)
• Stroke is also a leading cause of functional
impairments, with 20% of survivors requiring
institutional care after 3 months and 15% to 30%
being permanently disabled.
 RISK FACTORS FOR ISCHEMIC STROKE

Nonmodifiable risk factors or Modifiable, well documented

risk markers
 Age (doubling each 10 years over age 55). Hypertension. Single most important
 Gender (men>women). risk factor for ischemic stroke.
 Race (blacks>Hispanics>whites).  Atrial fibrillation. Most important
 Family history of stroke and
(paternal>maternal). treatable cardiac cause of stroke
 Low birth weight (<2,500 g).  Other cardiac diseases.
 Diabetes. Independent risk factor.
Potentially modifiable, less well  Dyslipidemia.
documented  Cigarette smoking
 Alcohol
 Oral contraceptives.  Sickle cell disease
 Migraine.  Asymptomatic carotid stenosis.
 Drug and alcohol abuse.  Post menopausal hormonal therapy.
Hemostatic and inflammatory factors –  Life style factors.
fibrinogen linked to increased risk.  Obesity,
 Homocysteine.  Diet
 Sleep disordered breathing.  physical inactivity.

6
• Homocysteine is a common amino acid in your blood. You get it
mostly from eating meat. High levels of it are linked to early
development of heart disease.
PATHOPHYSIOLOGY OF ISCHEMIC STROKE

 In carotid atherosclerosis:
 Plaque formation  plaque rupture  clot formation can cause local
occlusion or lead to embolism  lodging downstream in a cerebral artery.
 In the case of cardiogenic embolism:
 stasis of blood in the atria or ventricles of the heart  formation of local
clots that can become dislodged and travel directly through the aorta to
the cerebral circulation  arterial occlusion

 Arterial occlusion  decreasing cerebral blood flow and

causing ischemia distal to the occlusion and the impairment
cerebral autoregulation.

7
 Clinical Presentation
J.S a 55-year-old, 167 cm , 85-kg man, experienced a
rapidly progressive paralysis of his right arm and
slurred speech yesterday.
These symptoms lasted for 15 to 20 minutes and
resolved rapidly. neurologic examination is entirely
normal, and he denies any feeling of weakness,
He smokes 2 packs of cigarettes daily and drinks 3
to 6
cans of beer each evening. His physical
examination is
entirely normal except for *, which was first noted
2
years ago. His blood pressure (BP) is 165/100 mm
Hg,
and he has a long history of hypertension. A
Doppler
examination of his carotid arteries shows a
90% 8
Clinical Presentation
• Sudden weakness, paralysis, numbness of face, arm, leg on 1 or both
sides
• Loss of speech (aphasia)
• Dimness, loss of vision
• Dizziness, falls, unsteadiness
• Severe headache
• Loss of consciousness
10
Clinical Presentation
Definitions:
• Hemiplegia: paralysis affecting one side of body
• Hemiparesis: Weakness (partial paralysis) affecting one side of the
body
• Hemiparesthesia: abnormal sensation of one side of body
• Apraxia: inability to carry out familiar, purposeful movements such as
dressing oneself
• Ataxia: motor coordination fails or becomes unstable
• Aphasia: loss of expression by speech, writing, or comprehension
• Dysarthria: slurred speech
• Diplopia: double vision
• monocular visual loss (amaurosis fugax): sudden temporary
blindness
• Dysphagia: difficulty swallowing
12
Blood Disorders
• Consider in patients < 45 yo , patients with history of clotting
dysfunction and patients with history of cryptogenic stroke
- Sickle Cell Anemia
- Polycythemia vera
- Essential thrombocytosis The function of protein S is to inactivate
- HIT factor Va and factor VIIIa. This function
is carried out directly by protein C,
- Protein C or S deficiency and protein S serves as a cofactor
- Prothrombin gene mutation
- Factor V Leiden mutation (factor V facilitate factor
Xa-
induced conversion of prothrombin to thrombin)
- Antithrombin III deficiency
- Antiphospholipid syndrome (APLS) (Lupus and
anticardiolipin AB)
- Hyperhomocysteinemia
14
Diagnostic Tests
• MRI

- Will reveal areas of ischemia with higher resolution and earlier than
CT

• Carotid Doppler

- Shows degree of stenosis of carotid arteries supplying blood to the

brain

• ECG

- Heart rhythm
 Diagnostic Tests
• Transthoracic echocardiography (TTE)

- Valve or wall motion abnormalities

• Transesophageal echocardiography (TEE)

- Use to determine whether there is a thrombus in the left atrium

- Can also visualize the aortic arch

• Transcranial Doppler US

- Determines intracranial stenosis

• A transesophageal echo (TEE) test is a type of echo that uses a long,
thin, tube (endoscope) to guide the ultrasound transducer down the
esophagus (“food pipe” that goes from the mouth to the stomach).

• A transthoracic echocardiogram (TTE) is the most common type

of echocardiogram, which is a still or moving image of the internal
parts of the heart using ultrasound. In this case, the probe (or
ultrasonic transducer) is placed on the chest or abdomen of the
subject to get various views of the heart.
 Primary Prevention

 Carotid endarterectomy (CEA) is a surgical procedure used to prevent

stroke, by correcting stenosis (narrowing) in the common carotid artery.
Endarterectomy is the removal of material on the inside (end-) of an
artery.
Primary Prevention
Aspirin

“The use of aspirin for cardiovascular (including but not specific to stroke)
prophylaxis is reasonable for people whose risk is sufficiently high (10-
year risk >10%) for the benefits to outweigh the risks associated with
treatment. A cardiovascular risk calculator to assist in estimating 10-year
risk can be found online at http://my.americanheart.org/cvriskcalculator
(Class IIa; Level of Evidence A).”

Guidelines for the Primary Prevention of Stroke: A Statement for Healthcare Professionals From the
American Heart Association/American Stroke Association published online October 28, 2014
Primary Prevention
Atrial Fibrillation
Stroke risk stratification based on CHA2DS2-VASc score
Condition Points Annual Stroke Risk
Congestive heart failure (or Left CHA2DS2-VASc Score Stroke Risk % 95% CI
C ventricular systolic dysfunction) 1

Hypertension: blood pressure 0 0 -

H consistently above 140/90 mmHg (or 1 1 1.3 -
treated hypertension on medication)
2 2.2 -
A2 Age ≥75 years 2
3 3.2 -
D Diabetes Mellitus 1
4 4.0 -
S2 Prior Stroke or TIA or thromboembolism 2
5 6.7 -
Vascular disease (e.g. peripheral artery
V disease, myocardial infarction, aortic 1 6 9.8 -
plaque) 7 9.6 -
A Age 65–74 years 1 8 12.5 -
Sc Sex category (i.e. female sex) 1 9 15.2 -
Primary Prevention
Atrial Fibrillation
Stroke risk stratification based on CHA2DS2-VASc score
Anticoagulation
Score Risk Therapy Considerations

0 (male) or 1 No anticoagulant
(female) Low therapy No anticoagulant therapy

Oral anticoagulant, with well controlled Vitamin

Oral anticoagulant K Antagonist (VKA, e.g. warfarin with time in
1 (male) Moderate should be therapeutic range >70%), or a Non-VKA Oral
considered Anticoagulant (NOAC, e.g. dabigatran,
rivaroxaban, edoxaban or apixaban)

Oral anticoagulant, with well controlled Vitamin

K Antagonist (VKA, e.g. warfarin with time in
Oral anticoagulant is therapeutic range >70%), or a Non-VKA Oral
2 or greater High recommended Anticoagulant (NOAC, e.g. dabigatran,
rivaroxaban, edoxaban or apixaban)
Primary Prevention
Bleeding Risk stratification cased on HAS-BLED score
 Developed to assess 1-year risk of major bleeding in patients with
A.fib
- Major bleeding: intracranial bleeding, hospitalization, hemoglobin
decrease > 2 g/dL, and/or transfusion
Primary Prevention
Atrial Fibrillation

• RE-LY Study (Randomized Evaluation of Long-Term

Anticoagulation Therapy Study):

- Dabigatran 110 mg twice daily was found to have similar incidence

of stroke but less bleeding when compared to warfarin

- Dabigatran 150 mg twice daily lowered the incidence of stroke

or systemic embolism but had similar bleeding when
compared to warfarin

• When warfarin is used as the anticoagulant of choice for Afib

, target INR of 2-3
 Primary Prevention of Ischemic Stroke
Factor Goal Recommendation
Hypertension Blood Pressure <140/90 Follow JNC 7 guidelines; after
mmHg; with diabetes lifestyle modification
<130/80 thiazide-type diuretic,
angiotensin converting
enzyme inhibitor, or
angiotensin receptor blocker

Atrial fibrillation When warfarin is used Aspirin 75–325 mg/day or

INR 2–3 warfarin as determined by
the use of the CHADS2 score

Dyslipidemia National Cholesterol Lifestyle modification, HMG

Education Program III CoA reductase inhibitor
goals

Women (>65 years, history Reduce risk without Aspirin 75–325 mg/day; use
of hypertension, bleeding complications the lowest possible dose
hyperlipidemia, diabetes,
or 10-year cardiovascular
risk ≥10%)
23
 Primary Prevention of Ischemic Stroke
Factor Goal Recommendation
Cigarette smoke Elimination of cigarette Smoking cessation;
smoke avoidance of
environmental tobacco
smoke

Physical inactivity ≥30 minutes daily of Establish exercise program

moderate intensity activity of aerobic activity
Excessive alcohol intake Moderation ≤2 drinks/day for men or
≤1 drink/day for
nonpregnant women

Diet and nutrition ≤2.3 g/day of sodium; ≥4.7 Institute a diet that is high
g/day of potassium in fruits and vegetables and
low in saturated fats

Elevated lipoprotein(a) Reduction of lipoprotein(a) Niacin 2,000 mg/day as

by ≥25% tolerated

24
Acute Treatment
The goals of treatment of acute stroke are

(1) to reduce the ongoing neurologic injury and

decrease mortality and long-term disability.

(2) prevent complications secondary to immobility

and neurologic dysfunction.

(3) prevent stroke recurrence.

25
Treatment Timeline

Time Target

Door to Doctor 10 mins

Access to Neuro Expertise 15 min

Door to CT scan completion 25 min

Door to CT scan 45 min

interpretation

Door to Treatment (needle) 60 min

Admission to Stroke Unit or 3 hrs

ICU
 GP IIb/IIIa
antagonists
Acute Surgical Treatment
Ischemic Stroke

• Surgical treatment in the acute phase are limited

• Craniectomy
- Releases pressure when a patient has cerebral edema due to a large
infarction
• Endovascular embolectomy
- Done in combination with IA thrombolysis with tPA
The essentials of t-PA treatment protocol can be summarized
as:
(1) stroke team activation,
(2) onset of symptoms within 3 hours (new: expansion to 4.5 hours),
(3) CT scan to rule out hemorrhage,
(4) meet inclusion and exclusion criteria (Table 22–3),
(5) administer t-PA 0.9 mg/kg over 1 hour, with 10% given as initial
bolus over 1 minute,
(6)avoid antithrombotic (anticoagulant or antiplatelet) therapy for 24
hours.
(7) Monitor the patient closely for response and hemorrhage.

Early aspirin therapy also has been shown to reduce long-term death
and disability but should never be given within 24 hours of the
administration of t-PA because it can increase the risk of
bleeding in such patients.

29
Thrombolytic therapy aimed to reduce death
and neurologic debits when treatment was
initiated with 6 hours of symptom onset [odds
ratio, 0.83; 95% confidence interval, 0.73 to 0.94)

and within 3 hours of symptom onset (odds

ratio, 0.58; 95% confidence interval, 0.46 to
0.74). This analysis substantiates the use of PA in
the treatment of ischemic stroke.

30
Fibrinolytics

Recombinant Tissue Plasminogen Activator (r-tPA)-

Alteplase/Activase®

• Grade IA recommendation
• IV tPA when used within 3 hours of symptom onset reduces disability
caused by stroke ………….> intraarterial can be given within < 6 h
- Recently extended to 4.5 hours with additional exclusion criteria
• 0.9 mg/kg (max 90 mg) over 1 hour
- 10% of dose given as an initial bolus over 1 minute
• Use actual body weight to calculate dose
• Remove excess from bottle to avoid overdosing
• Symptomatic intracerebral hemorrhage can occur in 6% of patients
 Criteria for Alteplase Use in Treatment of Acute Stroke
Inclusion Criteria
• 18 years of age or older
• Clinical diagnosis of stroke with
clinically meaningful neurologic
deficit
• with the onset of symptoms
<4.5 hours before beginning
treatment; if the exact time of
stroke onset is not known, it is
defined as the last time the
patient was known to be normal
• Baseline CT with no evidence of
intracranial hemorrhage
Exclusion Criteria
• Minor or rapidly improving symptoms
• CT signs of intracranial hemorrhage
• History of intracranial hemorrhage
• Seizure at onset of stroke
• Stroke or serious head injury within 3 months
• Major surgery or serious trauma within
2 weeks
• GI or urinary tract hemorrhage within
3 weeks
• Systolic BP >185 mmHg, diastolic BP
>110
mmHg
• Aggressive treatment to lower BP
• Glucose 400 mg/dL
• Symptoms of subarachnoid
hemorrhage
32
Fibrinolytics
Recombinant Tissue Plasminogen Activator (r-tPA)-
Alteplase/Activase®

• Additional exclusion criteria for the 3-4.5 h time frame

- > 80 yo
- NIHSS score > 25 (National Institutes of Health Stroke Scale)
- Prior stroke + DM
- On anticoagulants regardless of INR
- Imaging evidence of ischemic injury involving more than one third of the
MCA (middle cerebral artery)

• Never beyond 4.5 hours

Fibrinolytics
Recombinant Tissue Plasminogen Activator (r-tPA)-
Alteplase/Activase®

• Monitoring
- Neurologic assessments every 15 minutes during infusion and then
every 30 minutes x 6 hours followed by hourly checks until 24 hours
after treatment
- Measure BP every 15 minutes x 2 hours; every 30 minutes x 6 hours
followed by hourly checks until 24 hours past alteplase initiation
- Obtain a follow-up CT scan at 24 hours prior to initiating antiplatelets
or anticoagulants
Neurological

D/C

BP

Invasive proc.

Anticoagulant
Fibrinolytics

Recombinant Tissue Plasminogen Activator (r-tPA)-

Alteplase/Activase®

• Intra-arterial tPA

- Beneficial for treatment of carefully selected patients with major

ischemic strokes of < 6 hours duration
- Only for patients who are Not candidates for IV tPA
- Seen most often with acute basilar artery and MCA occlusion
- Total dose usually 1/3 of the IV dose
- tPA is not FDA approved for intra-arterial use
 Patients with elevated blood pressure should remain untreated unless
their blood pressure exceeds 220/120 mm Hg or they have evidence of
aortic dissection, acute myocardial infarction (AMI), pulmonary
edema, or hypertensive encephalopathy (WHY?)

 If blood
pressure is
treated, short-
acting
parenteral
agents, such as
labetalol /
nicardipine /
nitroprusside,
are favored.

37
38
 Aspirin in Patients With Acute Ischemic Stroke

• In patients with acute ischemic stroke or transient ischemic

attack (TIA), we recommend early (within 48 h) aspirin
therapy at a dose of 160 to 325 mg over no aspirin therapy
(Grade 1A).

Anticoagulation in Patients With Acute Ischemic Stroke

• In patients with acute ischemic stroke or TIA, we recommend

early (within 48 h) aspirin therapy with an initial dose of 160 to
325 mg over therapeutic parenteral anticoagulation (Grade
1A).
 Secondary Prevention of Noncardioembolic Stroke
• In patients with a history of noncardioembolic ischemic stroke or TIA,
we recommend
• long-term treatment with aspirin (75-100 mg once daily)
• clopidogrel (75 mg once daily),
• aspirin/extended-release dipyridamole (25 mg/200 mg bid),
• cilostazol (100 mg bid) …>
used when we want more perfusion to the legs but it has some
side effects !!

over no antiplatelet therapy (Grade 1A), oral anticoagulants

(Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B),
or triflusal (Grade 2B).

• Of the recommended antiplatelet regimens, we suggest clopidogrel or

aspirin/extended release dipyridamole over aspirin (Grade 2B) or
cilostazol (Grade 2C).
 Secondary Prevention of Cardioembolic Stroke
• In patients with a history of ischemic stroke or TIA and atrial fibrillation (AF),
including paroxysmal AF, we recommend oral anticoagulation over no antithrombotic
therapy (Grade 1A), aspirin (Grade 1B), or combination therapy with aspirin and
clopidogrel (Grade 1B).

• In patients with a history of ischemic stroke or TIA and atrial fibrillation,

including paroxysmal AF, we suggest oral anticoagulation with dabigatran 150
mg bid over adjusted-dose VKA therapy (target range, 2.0-3.0)

• In patients with a history of ischemic stroke or TIA and atrial fibrillation, including
paroxysmal AF, who are unsuitable for or choose not to take an oral anticoagulant (for
reasons other than concerns about major bleeding), we recommend combination
therapy with aspirin and clopidogrel over aspirin (Grade 1B).

• Remarks: Patients should be treated (ie, bridged) with aspirin until anticoagulation
has reached a therapeutic level.
• - warfarin is better than dapigatran if there is‫ص;;مام; ص;;ناعي‬
• - warfarin C.I in liver failure , dapigatran C.I renal failure.
In secondary prevention, carotid endarterectomy
of an ulcerated and/or stenotic carotid artery is a very
effective way to reduce stroke incidence and
recurrence in appropriate patients and in centers
where the operative morbidity and mortality are low.

In fact, in ischemic stroke patients with 70% to 99%

stenosis of an ipsilateral internal carotid artery,
recurrent stroke risk can be reduced by up to 48%
compared with medical therapy alone when
combined with aspirin 325 mg daily.
42
Patient monitoring

43