13

CHAPTER
Stroke

• Stroke involves abrupt onset of focal neurologic deficit that lasts at least 24 hours and
is presumed to be of vascular origin. Stroke can be either ischemic or hemorrhagic.
Transient ischemic attacks (TIAs) are focal ischemic neurologic deficits lasting less
than 24 hours and usually less than 30 minutes.

PATHOPHYSIOLOGY
ISCHEMIC STROKE
• Ischemic strokes (87% of all strokes) are due either to local thrombus formation or
emboli occluding a cerebral artery. Cerebral atherosclerosis is a cause in most cases,
but 30% are of unknown etiology. Emboli arise either from intra- or extracranial
arteries. Twenty percent of ischemic strokes arise from the heart.
• Carotid atherosclerotic plaques may rupture, resulting in collagen exposure, platelet
aggregation, and thrombus formation. The clot may cause local occlusion or dislodge
and travel distally, eventually occluding a cerebral vessel.
• In cardiogenic embolism, stasis of blood flow in the atria or ventricles leads to for-
mation of local clots that can dislodge and travel through the aorta to the cerebral
circulation.
• Thrombus formation and embolism result in arterial occlusion, decreasing cerebral
blood flow and causing ischemia and ultimately infarction distal to the occlusion.
HEMORRHAGIC STROKE
• Hemorrhagic strokes (13% of strokes) include subarachnoid hemorrhage (SAH),
intracerebral hemorrhage, and subdural hematomas. SAH may result from trauma
or rupture of an intracranial aneurysm or arteriovenous malformation (AVM).
Intracerebral hemorrhage occurs when a ruptured blood vessel within the brain
causes a hematoma. Subdural hematomas are usually caused by trauma.
• Blood in the brain parenchyma damages surrounding tissue through a mass
effect and the neurotoxicity of blood components and their degradation products.
Hemorrhagic stroke can result in abrupt increased intracranial pressure leading to
herniation and death.

CLINICAL PRESENTATION
• Patients may be unable to provide a reliable history because of neurologic deficits.
Family members or other witnesses may need to provide this information.
• Symptoms include unilateral weakness, inability to speak, loss of vision, vertigo, or
falling. Ischemic stroke is not usually painful, but headache may occur in hemor-
rhagic stroke.
• Neurologic deficits on physical examination depend on the brain area involved.
Hemi- or monoparesis and hemisensory deficits are common. Patients with posterior
circulation involvement may have vertigo and diplopia. Anterior circulation strokes
commonly result in aphasia. Patients may experience dysarthria, visual field defects,
and altered levels of consciousness.

DIAGNOSIS
• Laboratory tests for hypercoagulable states should be done only when the cause
cannot be determined based on presence of risk factors. Protein C, protein S, and
antithrombin III are best measured in steady state rather than in the acute stage.
Antiphospholipid antibodies are of higher yield but should be reserved for patients
younger than 50 years and those who have had multiple venous or arterial throm-
botic events or livedo reticularis.

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• Computed tomography (CT) and magnetic resonance imaging (MRI) head scans can
reveal areas of hemorrhage and infarction.
• Carotid Doppler (CD), electrocardiogram (ECG), transthoracic echocardiogram
(TTE), and transcranial Doppler (TCD) studies can each provide valuable diagnostic
information.

TREATMENT
• Goals of Treatment: The goals are to (1) reduce ongoing neurologic injury and
decrease mortality and long-term disability, (2) prevent complications secondary to
immobility and neurologic dysfunction, and (3) prevent stroke recurrence.
GENERAL APPROACH
• Ensure adequate respiratory and cardiac support and determine quickly from CT
scan whether the lesion is ischemic or hemorrhagic.
• Evaluate ischemic stroke patients presenting within hours of symptom onset for
reperfusion therapy.
• Elevated blood pressure (BP) should remain untreated in the acute period (first 7 days)
after ischemic stroke to avoid decreasing cerebral blood flow and worsening symp-
toms. BP should be lowered if it exceeds 220/120 mm Hg or there is evidence of aortic
dissection, acute myocardial infarction (MI), pulmonary edema, or hypertensive
encephalopathy. If BP is treated in the acute phase, short-acting parenteral agents (eg,
labetalol, nicardipine, nitroprusside) are preferred.
• Assess patients with hemorrhagic stroke to determine whether they are candidates
for surgical intervention.
• After the hyperacute phase, focus on preventing progressive deficits, minimizing
complications, and instituting secondary prevention strategies.
NONPHARMACOLOGIC THERAPY
• Acute ischemic stroke: Surgical decompression is sometimes necessary to reduce
intracranial pressure. An interprofessional team approach that includes early reha-
bilitation can reduce long-term disability. In secondary prevention, carotid endarter-
ectomy and stenting may be effective in reducing stroke incidence and recurrence in
appropriate patients.
• Hemorrhagic stroke: In SAH, surgical intervention to clip or ablate the vascular abnormal-
ity reduces mortality from rebleeding. After primary intracerebral hemorrhage, surgical
evacuation may be beneficial in some situations. Insertion of an external ventricular drain
with monitoring of intracranial pressure is commonly performed in these patients.

PHARMACOLOGIC THERAPY OF ISCHEMIC STROKE

• Evidence-based recommendations for pharmacotherapy of ischemic stroke are given
in Table 13–1.
• Alteplase (t-PA, tissue plasminogen activator) initiated within 4.5 hours of symp-
tom onset reduces disability from ischemic stroke. Adherence to a strict protocol
is essential to achieving positive outcomes: (1) activate the stroke team; (2) treat as
early as possible within 4.5 hours of onset; (3) obtain CT scan to rule out hemorrhage;
(4) meet all inclusion and no exclusion criteria (Table 13–2); (5) administer alteplase
0.9 mg/kg (maximum 90 mg) infused IV over 1 hour, with 10% given as initial bolus
over 1 minute; (6) avoid anticoagulant and antiplatelet therapy for 24 hours; and
(7) monitor the patient closely for elevated BP, response, and hemorrhage.
• Aspirin 160 to 325 mg/day started between 24 and 48 hours after completion of
alteplase also reduces long-term death and disability.
• Secondary prevention of ischemic stroke:
✓ Use antiplatelet therapy in noncardioembolic stroke. Aspirin, clopidogrel, and
extended-release dipyridamole plus aspirin are all first-line agents (see Table 13–1).
Cilostazol is also a first-line agent, but its use has been limited by lack of data.
Limit the combination of clopidogrel and ASA to select patients with a recent MI
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TABLE 13–1 Recommendations for Pharmacotherapy of Ischemic Stroke

Recommendation Evidencea
Acute treatment Alteplase 0.9 mg/kg IV (max 90 mg) over 1 h in IA
select patients within 3 h of onset
Alteplase 0.9 mg/kg IV (max 90 mg) over 1 h IB
between 3 and 4.5 h of onset
Aspirin 160–325 mg daily started within 48 h of IA
onset
Secondary prevention
Noncardioembolic Antiplatelet therapy IA
Aspirin 50–325 mg daily IA
Clopidogrel 75 mg daily IIa B
Aspirin 25 mg + extended-release dipyridamole IB
200 mg twice daily
Cardioembolic (esp. Vitamin K antagonist (INR = 2.5) IA
atrial fibrillation) Dabigatran 150 mg twice daily 2B
Atherosclerosis Intense statin therapy IB
All patients BP reduction IA

BP, blood pressure; INR, international normalized ratio.

a
Classes of evidence: I, evidence or general agreement that treatment is useful and effective; II, con-
flicting evidence about usefulness; IIa, weight of evidence in favor of the treatment; IIb, usefulness
less well established.
Levels of evidence: A, multiple randomized clinical trials; B, a single randomized trial or nonrandom-
ized studies; C, expert consensus or case studies.

history or intracranial stenosis and only with ultra–low-dose ASA to minimize

bleeding risk.
✓ Oral anticoagulation is recommended for atrial fibrillation and a presumed cardiac
source of embolism. A vitamin K antagonist (warfarin) is first line, but other oral
anticoagulants (eg, dabigatran) may be recommended for some patients.
• Treatment of elevated BP after ischemic stroke reduces risk of stroke recurrence.
Treatment guidelines recommend BP reduction in patients with stroke or TIA after
the acute period (first 7 days).
• Statins reduce risk of stroke by approximately 30% in patients with coronary artery
disease and elevated plasma lipids. Treat ischemic stroke patients, regardless of base-
line cholesterol, with high-intensity statin therapy to achieve a reduction of at least
50% in LDL for secondary stroke prevention.
• Low-molecular-weight heparin or low-dose subcutaneous unfractionated heparin
(5000 units three times daily) is recommended for prevention of deep vein thrombo-
sis in hospitalized patients with decreased mobility due to stroke and should be used
in all but the most minor strokes.

PHARMACOLOGIC THERAPY OF HEMORRHAGIC STROKE

• There are no standard pharmacologic strategies for treating intracerebral hemor-
rhage. Follow medical guidelines for managing BP, increased intracranial pressure,
and other medical complications in acutely ill patients in neurointensive care units.
• SAH due to aneurysm rupture is often associated with delayed cerebral ischemia
in the 2 weeks after the bleeding episode. Vasospasm of the cerebral vasculature is
thought to be responsible for the delayed ischemia and occurs between 4 and 21 days
after the bleed. The calcium channel blocker nimodipine 60 mg every 4 hours for
21 days, along with maintenance of intravascular volume with pressor therapy, is
recommended to reduce the incidence and severity of neurologic deficits resulting
from delayed ischemia.
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TABLE 13–2 Inclusion and Exclusion Criteria for Alteplase Use in Acute Ischemic Stroke
Inclusion Criteria (all YES boxes must be checked before treatment)
YES
  ❏ Age ≥18 years
  ❏ Clinical diagnosis of ischemic stroke causing a measurable neurologic deficit
  ❏ Time of symptom onset well established to be <4.5 h before treatment would begin
Exclusion Criteria (all NO boxes must be checked before treatment)
NO
  ❏ Evidence of intracranial hemorrhage on noncontrast head CT
  ❏ Only minor or rapidly improving stroke symptoms
  ❏ High clinical suspicion of SAH even with normal CT
  ❏ Active internal bleeding (eg, GI/GU bleeding within 21 days)
  ❏ Known bleeding diathesis, including, but not limited to, platelet count <100,000/mm3
(<100 × 1012/L)
  ❏ Patient has received heparin within 48 h and had an elevated aPTT
  ❏ Recent use of anticoagulant (eg, warfarin) and elevated PT (>15 s)/INR
  ❏ Intracranial surgery, serious head trauma, or previous stroke within 3 months
  ❏ Major surgery or serious trauma within 14 days
  ❏ Recent arterial puncture at noncompressible site
  ❏ Lumbar puncture within 7 days
  ❏ History of intracranial hemorrhage, AVM, or aneurysm
  ❏ Witnessed seizure at stroke onset
  ❏ Recent acute myocardial infarction
  ❏ SBP >185 mm Hg or DBP >110 mm Hg at time of treatment
Additional exclusion criteria if within 3–4.5 h of onset:
  ❏ Age >80 years
  ❏ Current treatment with oral anticoagulants
  ❏ NIH stroke scale >25 (severe stroke)
  ❏ History of both stroke and diabetes
a
PTT, activated partial thromboplastin time; AVM, arteriovenous malformation; CT, computed tomog-
raphy; DBP, diastolic blood pressure; GI, gastrointestinal; GU, genitourinary; INR, international
normalized ratio; NIH, National Institutes of Health; PT, prothrombin time; SAH, subarachnoid
hemorrhage; SBP, systolic blood pressure.

EVALUATION OF THERAPEUTIC OUTCOMES

• Monitor patients with acute stroke intensely for development of neurologic worsen-
ing (recurrence or extension), complications (thromboembolism, infection), and
adverse treatment effects.
• The most common reasons for clinical deterioration in stroke patients include: (1) exten-
sion of the original lesion in the brain, (2) development of cerebral edema and raised
intracranial pressure, (3) hypertensive emergency, (4) infection (eg, urinary and
respiratory tract), (5) venous thromboembolism, (6) electrolyte abnormalities and
rhythm disturbances, and (7) recurrent stroke. The approach to monitoring stroke
patients is summarized in Table 13–3.

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SECTION 2   |   Cardiovascular Disorders

TABLE 13–3 Monitoring Hospitalized Acute Stroke Patients

Treatment Parameter(s) Frequency
Ischemic stroke Alteplase BP, neurologic function, Every 15 min × 1 h; every 0.5
bleeding h × 6 h; every 1 h × 17 h;
every shift after
Aspirin Bleeding Daily
Clopidogrel Bleeding Daily
ERDP/ASA Headache, bleeding Daily
Warfarin Bleeding, INR, Hb/Hct INR daily × 3 days; weekly
until stable; monthly
Dabigatran Bleeding Daily
Hemorrhagic BP, neurologic function, Every 2 h in ICU
stroke ICP

Nimodipine BP, neurologic function, Every 2 h in ICU

(for SAH) fluid status
All patients Temperature, CBC Temperature every 8 h; CBC
Pain (calf or chest) daily
Electrolytes and ECG Every 8 h
Up to daily
Heparins for DVT Bleeding, platelets Bleeding daily, platelets if
prophylaxis suspected thrombocy-
topenia

BP, blood pressure; CBC, complete blood cell count; DVT, deep vein thrombosis; ECG, electrocardio-
gram; ERDP/ASA, extended-release dipyridamole plus aspirin; Hb, hemoglobin; Hct, hematocrit;
ICP, intracranial pressure; ICU, intensive care unit; INR, international normalized ratio; SAH, sub-
arachnoid hemorrhage.

See Chapter 10, Stroke, authored by Susan C. Fagan and David C. Hess, for a more
detailed discussion of this topic.
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