a. Definitions. A stroke is an acute focal neurologic deficit produced by a disturbance in cerebral circulation that results from ischemic infarction, hemorrhage, or both. If the deficit resolves quickly and there is no evidence of infarction on imaging, the incident is a transient ischemic attack (TIA).
b. Epidemiology. Stroke is the fifth leading cause of death and the leading cause of severe disability in the United States. Mortality rates from stroke have fallen by more than 50% in the past 30 years, likely owing to improved risk factor control.
B. Causes of Stroke
a. Ischemic infarction
i. Distribution. Cerebral infarcts can be classified according to the type of vessel involved.
1. Small vessel. Chronic stress to vessels produces lipohyalinosis, leading to stenosis and occlusion.
2. Large vessel. Stroke in the distribution of a named blood vessel (e.g., middle cerebral artery). Strokes in these vascular territories can be caused by either (1) embolism from a vessel, valve, cardiac chamber or atherosclerotic plaque; or (2) inadequate perfusion due to vessel narrowing/stenosis.
3. Watershed infarctions are so-called because they occur in areas where blood supply is scarce and vulnerable. These often occur at the junction of the anterior and middle cerebral arteries or the junction of the posterior and middle cerebral arteries during systemic hypotension.
4. Venous. Thrombosis occurring in the superior sagittal sinus or other large cerebral veins may also result in cerebral infarction. Dural sinus thrombosis is often associated with malignancy or hyperviscosity syndromes.
ii. Source. Small-vessel, large-vessel, watershed, and venous infarctions may be produced by local processes or disease in the systemic circulation. It is helpful to remember the sources of infarcts by beginning in the arterioles of the brain, working backward to the heart and then through the venous system to the brain again (Table 86.1). Typical vascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking) are the key proximate causes of most strokes, and careful review of these factors is essential.
Table 86.1 Sources of Cerebral Infarcts
Other Risk Factors/Causes
Large and medium arteries
Dissection, Asian descent, vasculitis
Glucose, HbA1C, cholesterol panel, ESR, toxicology screen, MRA, CTA, or angiography
Glucose, HbA1C, cholesterol panel, MRA, CTA, Doppler ultrasound, or angiography
History of anterior myocardial infarction, ejection fraction <30%
EKG, cardiac monitoring, echocardiogram
Abnormal or prosthetic valves, endocarditis
Echocardiogram, ESR, blood cultures
Atrial fibrillation, left atrial enlargement, myxoma
EKG, cardiac monitoring, echocardiogram
Coronary artery disease, arrhythmia, shock
EKG, cardiac monitoring, CBC
Large or small vessel arterial
Polycythemia, sickle cell, antiphospholipid antibody syndrome, hyperviscosity syndrome
Anticardiolipin antibody, Russell’s viper venom test, antiphospholipid antibodies, viscosity studies
Deep venous thrombosis with patent foramen ovale or atrial septal defect (paradoxical embolism)
Echocardiogram with contrast, lower extremity Doppler ultrasound
Cerebral veins or sinuses
Dehydration, hypercoagulable state, otitis, sinusitis
Magnetic resonance venogram, conventional venogram. venous hypercoagulability evaluation
Hb = hemoglobin; CBC = complete blood count; CTA = computed tomographic angiogram; EKG = electrocardiogram; ESR = erythrocyte sedimentation rate; MRA = magnetic resonance angiogram.
i. Intracerebral hemorrhage is usually caused by hypertension. An underlying vascular malformation, cerebral amyloid angiopathy, or tumor may also result in intraparenchymal hemorrhage.
ii. Subarachnoid hemorrhage is usually caused by ruptured cerebral aneurysms when diagnosed in the absence of head trauma. A thunderclap onset of headache and neck stiffness is characteristic.
iv. Epidural hematoma is almost always sudden and posttraumatic.
v. Hemorrhagic transformation is said to occur when bleeding occurs into an ischemic infarct.
C. Approach to the Patient
a. Consider differential diagnoses
i. Reemergence of prior stroke symptoms. In patients with prior stroke and partial or complete recovery, symptoms can reemerge in the context of infectious, metabolic or otoxic insults.
iii. Postictal state. Focal weakness following a seizure (e.g., Todd’s paralysis) is occasionally seen.
iv. Hypertensive encephalopathy
v. Hypoglycemia or other severe metabolic derangements
Hypoglycemia is a stroke mimic: A stroke is never a stroke until it has had “50 of D50.”
vi. Infarction. In the first 6 hours after ischemic infarction, head computed tomography (CT) may be unrevealing; therefore, the patient history and physical examination findings are particularly important. Localization of the lesion helps to identify the infarction as large vessel, small vessel, watershed, or venous, thereby limiting the differential diagnosis and directing treatment. Table 86.2 summarizes the clinical manifestations and findings on imaging studies for each type of cerebral infarct.
Table 86.2 Classic Clinical Manifestations of Cerebral Infarcts
Lacunar syndrome (e.g., pure motor hemiparesis, ataxic hemiparesis, pure sensory deficit, clumsy hand dysarthria)
Small, often round, lesions in the white matter, deep gray matter, and brainstem
Middle cerebral artery (MCA)
Hemiparesis and hemisensory deficit (face = arm > leg), visual field cut, gaze preference, aphasia (left hemisphere) or neglect (right hemisphere)
Infarction in wedge of cortex and underlying white matter in frontal, temporal, or parietal lobes, usually along lateral aspect of the brain
Anterior cerebral artery (ACA)
Hemiparesis and hemisensory deficit (leg > arm, sparing face), gaze preference
Midline cortical/subcortical infarction
Signs of middle cerebral artery (MCA) infarct plus or minus signs of anterior cerebral artery (ACA) infarct or amaurosis fugax (sudden bilateral loss of vision).
ACA + MCA
Posterior cerebral artery (PCA)
Visual field cut (hemianopsia)
Occipital, mesial temporal, thalamic infarction
Cranial nerve palsies, ataxia, coma
“Man in the barrel” with proximal arm and leg weakness and numbness
Infarction in cortex and underlying white matter in a line from eyes to occiput
Variable; headache often present; legs often affected
Infarction and hemorrhage near the superior sagittal sinus or in the temporal lobe
vii. Hemorrhages will usually be apparent immediately using CT or MRI, although lumbar puncture is required to rule out subarachnoid hemorrhage, which may not be seen on imaging.
b. Search for an underlying cause
i. Almost all patients should undergo the studies summarized in Table 86.3. Local practice varies greatly regarding whether patients with TIA need to be admitted to the hospital for evaluation or observation.
Table 86.3 Initial Workup for the Evaluation of Stroke Patients
CBC, PT, PTT
Rule out hematologic problem
Rule out arrhythmia, myocardial infarction
Head CT or MRI scan
Rule out nonstroke, differentiate ischemic infarction from hemorrhage*
CBC = complete blood count; CT = computed tomography; EKG = electrocardiogram; ESR = erythrocyte sedimentation rate; MHA-TP = microhemagglutination–Treponema pallidum; MRI = magnetic resonance imaging; PT = prothrombin time; PTT = partial thromboplastin time.
* Head CT may not show evidence of ischemic infarction until 6 hours after infarction but is relatively sensitive for hemorrhage immediately. Contrast is rarely helpful. MRI is more sensitive for ischemic infarct, especially in the brainstem and cerebellum where bone obscures the CT view, but is more expensive and time-consuming.
ii. Risk for stroke after TIA can be determined using the ABCD2 score:
Age > 60 (1 point)
Systolic Blood Pressure > 140 mm Hg (1 point)
Clinical features including speech impairment without weakness (1 point) or unilateral weakness (2 points)
Duration 10–59 minutes (1 point) or >60 minutes (2 points)
Diabetes mellitus (1 point)
The total score predicts the 2-day risk for stroke as follows: 0–1 point (0%); 2–3 points (1.3%); 4–5 points (4.1%); 6–7 points (8.1%). Hospital admission is warranted in patients who score 3 points or more.
iii. The following studies are indicated in specific circumstances:
1. Carotid Doppler ultrasound is indicated following a large-vessel TIA or stroke when endarterectomy or carotid stenting is being considered.
2. Cardiac echocardiography is indicated following a large-vessel TIA or stroke to evaluate for an intracardiac thrombus or shunt (i.e., patent foramen ovale)
3. CT angiography is often considered in the setting of an acute stroke when knowledge of intracranial vasculature may affect treatment.
4. Magnetic resonance angiography (MRA) of the head is indicated for patients with possible intracranial large-vessel disease or suspected arterial dissection. MRA of the neck can also confirm abnormal carotid Doppler ultrasound findings.
5. Conventional angiography may be appropriate if carotid endarterectomy is being considered and better images are desired. Conventional angiography is more sensitive for vasculitis, aortic dissection, or subarachnoid hemorrhage.
6. Transcranial Doppler ultrasound is often indicated for patients with possible intracranial large-vessel disease or vasospasm following subarachnoid hemorrhage.
7. Lumbar puncture is indicated if subarachnoid hemorrhage is a possibility and not visualized on CT scan.
8. Hypercoagulability studies (see Chapter 67) are appropriate in patients younger than 45 years with no other risk factors for stroke.
9. Toxicology screen in young patients with unexplained stroke is often appropriate to rule out cocaine or amphetamine use.
a. Ischemic infarction. Until recently, treatment of stroke was primarily supportive and focused on secondary prevention. However, novel therapies directed at dissolving clots and protecting the patient from cerebral ischemia are now commonly used.
i. Generally accepted therapies
1. Pharmacologic therapy
a. Warfarin reduces the risk for a recurrent event by approximately 65% in patients with a known cardiac source of embolus (e.g., atrial fibrillation, mechanical heart valve, mural thrombus). There is no evidence supporting empiric use of heparin in the setting of acute stroke.
b. Aspirin or another antiplatelet agent (clopidogrel) is usually indicated for stroke prophylaxis in patients who do not meet one of the above indications for warfarin.
c. Tissue plasminogen activator (t-PA). Intravenous administration of t-PA may be beneficial for patients with a cerebral infarction who can be treated within 3 hours of symptom onset (defined as the time the patient can be last confirmed to be normal). Although current evidence suggests that this treatment does not decrease mortality. t-PA has been shown to improve the relative rate of neurologic recovery at 3 months by up to 50%. Importantly, t-PA may be associated with a 6% risk for serious intracranial hemorrhage (50% of which were fatal).
2. Supportive measures
a. Hold or decrease antihypertensive agents in order to allow for cerebral autoregulation. Consider intravenous hydration to increase blood flow to the ischemic area around the infarct.
b. Aspiration should be prevented by keeping the head of the bed elevated and having a speech pathologist evaluate patients with dysarthria or poor cough. Urinary tract infection should be prevented by removing urinary catheters as early as possible. Deep vein thrombosis should be prevented through use of prophylactic doses of unfractionated or low-molecular-weight heparin.
3. Secondary prevention
a. Atorvastatin, 80mg, should be started acutely after ischemic stroke in patients with a low-density lipoprotein (LDL) cholesterol level >100. Statins reduce the risk for recurrent stroke.
b. Smoking cessation counseling is mandatory in all stroke patients.
c. After the acute period, treatment of hypertension reduces recurrent stroke risk.
d. Diabetes mellitus should be tested for and, if present, treated.
4. Specific treatment that addresses the cause of the stroke (e.g., carotid endarterectomy) should be carried out if indicated.
5. Physical, occupational, and speech therapy are necessary.
ii. Evolving therapies
1. Anticoagulation. Antiplatelet agents and warfarin therapy continues to be reevaluated in a variety of clinical settings (e.g., aortic arch disease and cardiomyopathy with low ejection fraction).
2. Generally accepted therapies. Mechanical thrombectomy is highly beneficial for large artery occlusions (e.g., proximal MCA occlusion) if administered during cerebral angiogram within 6 hours of infarct onset, and for some patients up to 24 hours from onset with small areas of core infarction measured with perfusion imaging.
3. Neuroprotection. A variety of neuroprotective therapies (e.g., therapeutic cooling) are being investigated as a way of minimizing ischemic damage.
i. Hemorrhagic transformation. Treatment is the same as that for ischemic infarction, except heparin and aspirin are withheld until it is safe to resume these agents.
1. Blood pressure is usually lowered acutely to minimize risk for hematoma expansion.
2. Coagulopathy (e.g., warfarin therapy) should be reversed with fresh-frozen plasma or recombinant factor IX in addition to vitamin K.
3. Consultation with a neurosurgeon is warranted because surgical evacuation may be necessary depending on the size and location of the hemorrhage. In addition, placement of an external ventricular drain or other intracranial pressure monitor may also be necessary.
iii. Subarachnoid hemorrhage
1. Consultation with a neurosurgeon or interventional radiologist is indicated to explore the possibility of early aneurysm clipping or coiling. In addition, placement of an external ventricular drain may be necessary if there is acute hydrocephalus.
2. Before securing the aneurysm, blood pressure is usually lowered to minimize risk for rerupture. After the aneurysm is secured, blood pressure is often raised to prevent vasospasm.
3. Nimodipine therapy and hydration are indicated.
iv. Subdural and epidural hemorrhages. Consultation with a neurosurgeon to investigate the possibility of evacuation is appropriate.
Suggested Further Readings
Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med 2016;374:1533–42.Find this resource:
Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007;369:283–92.Find this resource:
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–8. (Classic Article.)Find this resource:
Prabhakaran S, Ruff I, Bernstein RA. Acute stroke intervention: a systematic review. JAMA 2015;313:1451–62.Find this resource:
van den Berg LA, Dijkgraaf MGW, Berkhemer OA, et al. Two-year outcome after endovascular treatment for acute ischemic stroke. N Engl J Med 2017;376:1341–9.Find this resource: