The brain and spinal cord can be affected by a variety of conditions related to the vascular system:

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  Ischemic stroke: lack of blood flow to a portion of the brain (or more rarely the spinal cord)

  
  
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  Intracranial or spinal hemorrhage at five possible sites:

  
  
  
  
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    Epidural hematoma: between the skull or spine and dura

    
    
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    Subdural hematoma: between the dura and arachnoid

    
    
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    Subarachnoid hemorrhage: between the arachnoid and brain or spinal cord

    
    
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    Intraparenchymal (intracerebral) hemorrhage: in the brain itself (or less commonly hemorrhage into the spinal cord (hematomyelia))

    
    
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    Intraventricular hemorrhage (within the ventricular system of the brain)

  
  
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  Cerebral venous sinus thrombosis

  
  
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  Vascular malformations

  
  
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  Vasculopathies, including vasculitis and reversible cerebral vasoconstriction syndrome (RCVS)

The term stroke refers to the clinical scenario in which a patient is “struck” by a sudden-onset neurologic deficit localizable to the brain (or more rarely the spinal cord; see “Vascular Diseases of the Spinal Cord”). The vascular conditions that are collectively referred to as stroke (or cerebrovascular accident) include ischemic stroke and intracerebral hemorrhage. Intracerebral hemorrhage is sometimes referred to as “hemorrhagic stroke.” Although subarachnoid hemorrhage is sometimes included as a cause of stroke, its clinical presentation and management are distinct from ischemic stroke and intracerebral hemorrhage. Although both ischemic stroke and intracerebral hemorrhage can present similarly, their management differs. Although the potential etiologies of ischemic stroke and intracerebral hemorrhage overlap, there are unique causes of each that must be considered.

Ischemic stroke and intracerebral hemorrhage both present with sudden-onset focal neurologic deficits, but intracerebral hemorrhage is more commonly accompanied by headache, nausea/vomiting, and depressed level of consciousness at onset due to increased intracranial pressure and brain displacement from mass effect of the hematoma. However, ischemic stroke may also present with headache, nausea/vomiting, and/or depressed level of consciousness depending on the size and location of the area of ischemia, so distinction between ischemic stroke and intracerebral hemorrhage often cannot be made on clinical grounds alone. Therefore, a CT scan is necessary for diagnosis as soon as stroke is suspected.

Acute management of ischemic stroke and acute management of intracerebral hemorrhage share many aspects of supportive care but differ with respect to two parameters: coagulation and blood pressure (Table 19–1). In acute ischemic stroke, the goals are to decrease thrombosis (thrombolysis, antiplatelet agents, or in some instances anticoagulation) and allow autoregulation of blood pressure (to restore/maintain tissue perfusion). In acute intracerebral hemorrhage, the goals are to stop bleeding (reversal of anticoagulation, administration of clotting factors) and reduce blood pressure (to decrease the likelihood of hematoma expansion).

Aside from these two parameters, the majority of acute supportive management and subsequent supportive care is shared between ischemic stroke and intracerebral hemorrhage:

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  Electocardiogram (ECG) and cardiac monitoring (to evaluate for myocardial infarction or arrhythmia, which can cause or be caused by stroke).

  
  
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  Evaluation of swallowing and prevention of aspiration.

  
  
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  Control of blood glucose to avoid hypoglycemia or hyperglycemia.

  
  
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  Maintenance of euthermia (by treating fever and underlying infection if it occurs).

  
  
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  Treatment of seizures if they occur (more common with intracerebral hemorrhage as compared to ischemic stroke).

  
  
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  Evaluation for and management of elevated intracranial pressure.

  
  
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  Early mobilization.

  
  
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  Deep venous thrombosis (DVT) prophylaxis. Pharmacologic DVT prophylaxis can be started immediately after ischemic stroke unless tissue plasminogen activator (tPA) is administered (in which case it is delayed 24 hours). However, pharmacologic DVT prophylaxis is generally not started until 24-48 hours after intracerebral hemorrhage. Mechanical prophylaxis can begin immediately after either type of stroke.

  
  
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  Physical therapy, speech therapy, and/or occupational therapy.

The types of neurologic deficits seen with ischemic stroke depend on the size and location of the infarct. A small infarct may cause symptoms so mild that the patient does not present for medical attention. This is borne out by the frequency with which evidence of a prior infarct is noted on a CT scan performed for other reasons in a patient with no known prior clinical history of stroke. However, a small infarct in the internal capsule or anterior pons could lead to contralateral hemiplegia. The stroke syndromes caused by infarction in the various vascular territories are discussed in Chapter 7 (see “Clinical Syndromes Associated with Cerebral Vascular Territories” in Chapter 7).

Transient Ischemic Attack

A transient ischemic attack (TIA) was initially defined as symptom of a stroke that last for less than 24 hours. However, the increased sensitivity of MRI with diffusion-weighted imaging (DWI) has demonstrated that many patients with transient stroke symptoms have actually had small strokes. Therefore, TIA is now defined as transient stroke symptoms that resolve completely without evidence of infarction on MRI. Most TIAs last for minutes to about an hour, and those that last longer often have evidence of infarction on DWI even if symptoms resolve completely. The risk of subsequent stroke after TIA can be estimated by the ABCD2 score (Johnston et al., 2007):

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  Age: 1 point if ≥60

  
  
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  Blood pressure: 1 point if ≥140/90 mm Hg at time of presentation

  
  
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  Clinical symptoms of TIA

  
  
  
  
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    2 points for unilateral weakness or

    
    
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    1 point for speech disturbance without weakness or

    
    
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    0 points for any other symptoms without weakness or speech disturbance

  
  
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  Diabetes: 1 point if present

  
  
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  Duration of TIA: 2 points for ≥60 minutes, 1 point for 10–59 minutes. 0 points if <10 minutes

A score of 1–3 yields a 2-day and 7-day stroke risk of approximately 1%, a score of 4–5 yields a 2-day stroke risk of approximately 4% and a 7-day stroke risk of approximately 6%, and a score of 6–7 yields a 2-day stroke risk of approximately 8% and a 7-day stroke risk of approximately 11% (Johnston et al., 2007). Some practitioners use this score to determine whether evaluation for etiology of TIA should proceed as an inpatient or can be performed in rapid outpatient follow up. Evaluation for etiology and stroke prevention after TIA is discussed with secondary prevention of stroke below.

Etiology of Ischemic Stroke

Understanding the potential etiologies of ischemic stroke allows for an understanding of the acute management, evaluation for etiology, and secondary prevention of ischemic stroke (Table 19–2). Any pathophysiologic process that disrupts blood supply to one or more regions of the brain can cause ischemic stroke. Anatomically, the blood supply to the brain begins in the left ventricle of the heart, travels through the aorta to the cervical vessels (carotid arteries and vertebral arteries), and ultimately passes through the cerebral arterial system. Pathology at any of these levels can lead to ischemic stroke, as can diseases of the blood itself. Therefore, the initial evaluation for stroke etiology (discussed in more detail below) must evaluate:

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  The arteries:

  
  
  
  
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    Ultrasound, CT angiogram (CTA), MR angiogram (MRA), or digital subtraction angiography

    
    
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    Evaluation for risk factors for arterial disease: blood pressure, blood sugar, lipids, smoking status

  
  
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  The heart: cardiac monitoring and echocardiogram

  
  
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  If clinically indicated, the blood; e.g., for hypercoagulability or sickle cell disease

Arterial Disease as a Cause of Ischemic Stroke

Diseases of the cerebral vasculature that can lead to ischemic stroke include:

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  Atherosclerosis and thromboembolic disease of the arteries

  
  
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  Lipohyalinosis of small penetrating arteries (small vessel disease)

  
  
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  Carotid or vertebral artery dissection

  
  
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  Cerebral vasospasm (e.g., reversible cerebral vasoconstriction syndrome [RCVS] or secondary to subarachnoid hemorrhage)

  
  
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  Vascular compression by an external mass (e.g., a neck tumor compressing one of the carotids)

  
  
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  Vasculopathy, including vasculitis, radiation-induced vasculopathy, moyamoya

Atherosclerosis and thromboembolic disease as a cause of ischemic stroke

Thrombosis refers to local formation of a clot in the lumen of a blood vessel. Embolism refers to passage of material from a more proximal source to a more distal location. In the case of the cerebral arteries, embolism may arise from the heart, the aortic arch, the cervical vessels (the carotid arteries or vertebral arteries), or from the venous circulation if there is a patent foramen ovale (see “Secondary Stroke Prevention in Patients With Patent Foramen Ovale” below). Atherosclerosis is the main cause of thrombotic disease of the cervical and cerebral blood vessels. Risk factors for atherosclerosis include hypertension, diabetes, hyperlipidemia, and smoking. Embolism from the carotid arteries or vertebral arteries to a more distal cerebral vessel is referred to as artery-to-artery embolism (e.g., from the internal carotid artery to the middle cerebral artery). Stroke can also be caused by embolism of thrombotic material from the heart to cerebral blood vessels (See “Cardiac Causes of Ischemic Stroke” below). If a patient has a patent foramen ovale, embolism from the venous circulation can cause stroke (paradoxical embolism). Rare causes of cerebral embolism not due to thromboembolism include air embolism, fat embolism, and amniotic fluid embolism.

Lipohyalinosis of small penetrating arteries as a cause of ischemic stroke—Chronic hypertension can lead to thickening of the walls of the small penetrating arteries (small vessel disease), which can predispose to lacunar infarcts in the deep subcortical regions (internal capsule or thalamus) or the anterior pons (see “Lacunar Strokes” in Chapter 7).

Cervical artery dissection as a cause of ischemic stroke—Cervical artery dissection is a tear between the layers of the wall of the cervical vessels (i.e., carotids or vertebral arteries). It is a common cause of stroke in the young and can be caused by head or neck trauma (which may be major or so minor that it cannot be recalled), chiropractic manipulation, and collagen disorders (e.g., Ehlers-Danlos, fibromuscular dysplasia). Cervical artery dissection can present as TIA or stroke, or may present with local symptoms such as neck pain, headache, and in the case of carotid artery dissection, lower cranial nerve palsies (cranial nerves 9–12) and/or Horner’s syndrome (in the case of internal carotid dissection only ptosis and miosis will be seen, but no anhidrosis because sweating fibers travel with the external carotid; see “Impaired Pupillary Dilatation” in Chapter 10). The risk of stroke is highest in the first week after dissection, and some patients may have multiple TIAs or strokes during this period. A dissected vessel has a flame-shaped appearance on CTA (Fig. 19–1A), and a crescentic intramural hematoma can be visualized on T1-weighted fat saturation MRI (Fig. 19–1B). Secondary stroke prevention in patients with TIA or stroke due to cervical artery dissection is discussed below (see “Secondary Stroke Prevention in Patients With Cervical Artery Dissection”).

Vasospasm as a cause of ischemic stroke—Vasospasm can be caused by:

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  Local irritation of the blood vessels by subarachnoid hemorrhage or meningitis

  
  
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  Failure of cerebral autoregulation, which can be seen in posterior reversible encephalopathy syndrome (PRES; see “Posterior Reversible Encephalopathy Syndrome” below) and eclampsia/postpartum angiopathy

  
  
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  Drugs such as cocaine and marijuana, and medications such as selective serotonin reuptake inhibitors (SSRIs) and sympathomimetic-containing cold medications can cause reversible cerebral vasoconstriction syndrome (RCVS; see “Reversible Cerebral Vasoconstriction Syndrome” below)

Vasculopathy and vasculitis as a cause of ischemic stroke—Beyond atherosclerosis, there are a number of other causes of vasculopathy that can cause ischemic stroke, including:

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  Radiation-induced vasculopathy (see “Neurotoxicity of Radiation Therapy” in Chapter 24)

  
  
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  Reversible cerebral vasoconstriction syndrome (RCVS), which can cause stroke or hemorrhage (most commonly subarachnoid hemorrhage when hemorrhage occurs)

  
  
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  Moyamoya (which can be primary or secondary)

  
  
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  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

  
  
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  Vasculitis: blood vessel inflammation that may be primary or secondary (e.g., secondary to infection or to a systemic vasculitic syndrome)

These and other vasculopathies are discussed below (see “Rarer Causes of Ischemic Stroke: Vasculopathies, Vasculitis, and Genetic Disorders”)

Cardiac Causes of Ischemic Stroke

Cardiac causes of stroke include:

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  Atrial fibrillation: clot formation due to stasis in the left atrium (especially the left atrial appendage) leads to cerebral embolism

  
  
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  Cardiac valvular disease (and mechanical cardiac valves)

  
  
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  Left ventricular failure with dilated left ventricle: clot formation due to stasis in the left ventricle leads to cerebral embolism

  
  
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  Myocardial infarction: due to development of left ventricular thrombus (mural thrombus)

  
  
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  Infective endocarditis with septic embolization

  
  
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  Nonbacterial thrombotic endocarditis (marantic endocarditis) with embolization, which can be caused by:

  
  
  
  
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    Inflammatory endocarditis in rheumatologic disease (e.g., Libman-Sacks endocarditis in lupus)

    
    
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    Malignancy causing thombus formation on cardiac valves (most common with mucin-secreting adenocarcniomas)

  
  
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  Cardiac tumors on which thrombus may form (e.g., fibroelastoma, atrial myxoma, metastasis)

  
  
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  Patent foramen ovale, which can serve as a conduit for thrombus formed in the venous circulation to find its way to the arterial system and cause stroke.

  
  
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  Cardiac arrest with hypoxic-ischemic injury. The gray matter is most sensitive to hypoxia, so hypoxic-ischemic injury can cause diffuse infarction of the cortex and/or basal ganglia (Fig. 19–2).

Hematologic Causes of Acute Ischemic Stroke

Problems with the blood itself can also lead to stroke:

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  Hypercoagulable states, which may be inherited (e.g., factor V Leiden mutation, prothrombin gene mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency) or acquired (e.g., antiphospholipid antibodies, hypercoagulability of malignancy, disseminated intravascular coagulation)

  
  
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  Sickle cell anemia

  
  
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  Hyperviscosity, which can be caused by polycythemia vera and Waldenström’s macroglobulinemia

  
  
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  Intravascular lymphoma

Initial Evaluation of a Patient With Acute Ischemic Stroke

The goal of the initial evaluation of a patient with a sudden-onset neurologic deficit is to establish whether the diagnosis is stroke and exclude potential “mimics” such as seizure/postictal state, migraine, unwitnessed head trauma, hypoglycemia or other acute metabolic abnormality, or intoxication. If a seizure is unwitnessed, the postictal confusion and/or Todd’s paralysis can mimic stroke. A migraine aura occurring for the first time may mimic stroke, especially before the classic headache emerges. Although acute metabolic derangements often present with global neurologic deficits rather than focal ones, focal findings can occur in the setting of hyperglycemia. Trauma and intoxications are generally apparent from the history and examination, but may require collateral information and toxicology screening (especially if a patient is simply “found down”). If a patient presents with acute left arm and face tingling, evaluation for myocardial infarction should be undertaken, since chest pain may not be a prominent feature of cardiac ischemia in elderly patients or patients with impaired pain perception due to diabetic neuropathy.

For any acute-onset neurologic deficit, monitoring of all vital signs is essential, and ECG, blood sugar, basic chemistries, complete blood count, and coagulation profile should be obtained while clinical evaluation is undertaken.

In practice, when acute stroke is suspected, history and examination are often performed en route to a CT scan since the use of thrombolytic treatment for acute ischemic stroke (IV tPA) requires rapid confirmation of the diagnosis and exclusion of alternative diagnoses within a very narrow time window (upper time limit of 3 hours or in some cases 4.5 hours from symptom onset, but the best outcomes are with earliest treatment). If CT reveals an alternative diagnosis—e.g., intracranial hemorrhage or tumor—the diagnostic and treatment approach shift accordingly.

Other important tests to obtain in addition to CT when considering thrombolytic therapy are serum platelets, plasma thromboplastin (PT), and partial thromboplastin time (PTT) to evaluate for a coagulopathy that would be a contraindication to such treatment. If CTA is to be performed, serum creatinine should also be measured to determine whether it is safe to administer intravenous contrast.

Neuroimaging Findings in Acute Ischemic Stroke

The CT scan may show no abnormalities in the acute setting of acute ischemic stroke since the CT hypodensity caused by ischemic stroke can take up to 12 hours to emerge. In some cases, however, subtle findings related to vessel occlusion or early ischemia may be seen on noncontrast CT in the acute setting: a hyperdense vessel (a sign of clot and/or slow flow in the vessel) (Fig. 19–3), blurring of the gray–white junction/sulcal effacement (Fig. 19–3), and, in middle cerebral artey (MCA) stroke, hypodensity of the insular ribbon (Fig. 19–4A). Early parenchymal hypodensity may be more easily visible when changing the window setting to 30-30 (Fig. 19–4B). If the clinical impression is that the patient is having an ischemic stroke, the CT scan does not reveal an alternative explanation for the patient’s symptoms, and the time of onset of symptoms is well established with the patient having presented within the 3-hour (or in some cases 4.5-hour) window, the patient can be considered for thrombolytic therapy if there are not contraindications (see “Thrombolysis in the Treatment of Acute Ischemic Stroke” below).

MRI with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences can demonstrate ischemic stroke within an hour after onset, and so MRI is much more sensitive than CT in the acute setting. Acute ischemic strokes appear bright on DWI and dark on ADC (Fig. 19–5). CTA can be performed to look for arterial occlusion that may be apparent before signs of tissue ischemia are visible on CT (Fig. 19–6). However, these studies take longer and may not be accessible acutely, and neither is required for the administration of IV tPA in the appropriate clinical setting. CTA and MRI may be performed acutely to determine whether a patient is a candidate for intra-arterial intervention (see “Thrombolysis in the Treatment of Acute Ischemic Stroke”).

Ischemic strokes do not become visible on fluid-attenuated inversion inversion recovery (FLAIR) imaging until about 6 hours from onset, so a stroke visible on diffusion sequences that is not yet visible on FLAIR is generally less than 6 hours from onset. ADC darkness is generally present for several days before normalizing, although DWI brightness may persist for approximately 7–10 days.

Although DWI/ADC sequences are believed to be the gold standard in stroke diagnosis, it should be noted that false negatives do occur in the first 24 hours, especially with strokes that are very small and/or in the posterior fossa.

Subacute strokes (about 1 week to 1 month old) can demonstrate enhancement on postcontrast CT or MRI (Fig. 19–7). This radiographic appearance may be mistaken for tumor if there is no clear clinical history of stroke, but subacute stroke can be radiologically distinguished from tumor in several ways: subacute strokes typically conform to a vascular territory, and usually demonstrate no or minimal surrounding edema or mass effect on surrounding structures as would be seen with tumors. In ambiguous cases, serial imaging should be performed to see if the lesion expands as would be expected with tumor, or develops volume loss (encephalomalacia) as would be expected with infarction.

Initial Treatment of Acute Ischemic Stroke

Since ischemic stroke is due to decreased blood supply to a region of the brain, the goal of therapy is restoration of brain perfusion. The two ways in which this is achieved are thrombolysis (if the patient meets criteria) and permissive hypertension (also called blood pressure autoregulation) or, in some cases, induced hypertension.

Thrombolysis in the Treatment of Acute Ischemic Stroke

Thrombolysis restores perfusion by aiding in the dissolution of occlusive thrombus. Thromboylsis may be achieved by administration of IV tPA and/or by catheter-based techniques (intra-arterial tPA or clot retrieval) if patients present early enough after stroke: up to 3–4.5 hours from the time of symptom onset for IV tPA; up to 6 hours for catheter-based techniques in the anterior circulation (longer durations from the time of symptom onset may be considered in the posterior circulation). The main risk of thrombolysis is symptomatic intracranial hemorrhage, which occurs in up to 6% of ischemic stroke patients treated within 3 hours. (The risk of hemorrhage is much lower in patients treated with tPA who are ultimately not found to have had an ischemic stroke; e.g., when migraine mimics stroke.)

Beyond presenting outside the time window, the main contraindications to IV tPA administration for ischemic stroke are those that would increase the risk of bleeding: coagulopathy (intrinsic or due to therapeutic anticoagulation), intracranial vascular malformation, prior intracerebral hemorrhage, recent major surgery or trauma (within 14 days), recent systemic (e.g., gastrointestinal) hemorrhage (within 21 days), recent stroke or head trauma (within 3 months), and blood pressure >185/110 mm Hg (although tPA can be administered if blood pressure can be brought to and sustained below this level with antihypertensive treatment).

Patients may be treated with IV tPA beyond 3 hours up to 4.5 hours after ischemic stroke onset unless they are older than 80 years old, have a prior history of stroke and diabetes, are on an anticoagulant (even if INR [international normalized ratio] is subtherapeutic), or if they have a very large stroke (National Institutes of Health [NIH] stroke scale score >25). Again, these are all factors that could increase the risk of bleeding complications in the setting of tPA administration.

If a patient presents within 6 hours of symptom onset in the setting of ischemic stroke in the anterior circulation and has evidence of a catheter-accessible vessel occlusion (e.g., distal internal carotid or proximal MCA), catheter-based therapies may be considered (intra-arterial tPA and/or clot retrieval) even if IV tPA has already been given. The time window for the posterior circulation is less well established; catheter-based therapies may be considered up to 12–24 hours after onset of stroke in the posterior circulation.

After receiving thrombolysis, patients must be monitored closely for 24 hours for symptoms/signs of intracerebral hemorrhage. In patients with no such signs, a CT scan is generally obtained 24 hours after IV tPA administration to evaluate for any asymptomatic hemorrhage. No antiplatelet agents or anticoagulants are administered during the 24-hour period after tPA administration, but may be administered after 24 hours if there is no clinical or radiologic evidence of intracranial hemorrhage. Blood pressure is kept below 180/105 mm Hg after tPA administration to reduce risk of intracranial hemorrhage.

Permissive Hypertension (Blood Pressure Autoregulation) and Induced Hypertension in the Treatment of Acute Ischemic Stroke

Patients with acute ischemic stroke are often hypertensive at presentation, which may be a physiologic response to attempt to restore/maintain perfusion of ischemic brain tissue through collaterals. For the first 24 hours after ischemic stroke, it is recommended that the blood pressure be allowed to autoregulate for this reason (permissive hypertension). Guidelines suggest allowing autoregulation up to 220/120 mm Hg if thrombolytic therapy is not given, or up to 180/105 mm Hg if thrombolysis is given, if systemically tolerated. Therefore, if a patient is taking oral antihypertensive agents at the time of acute ischemic stroke, these are generally withheld for the first 24 hours after stroke. After 24 hours, blood pressure is generally gradually lowered unless there is evidence of clinical worsening.

In some cases of large vessel occlusion (e.g., internal carotid or proximal MCA), patients may be noted to have worsening of their neurologic deficits at lower blood pressures, and improvement at higher blood pressures. This may occur with spontaneous fluctuation of blood pressure or with a trial of raising the blood pressure with a bolus of IV fluids when the blood pressure is lower than on initial presentation. In such blood pressure–dependent patients, maintaining the patient’s blood pressure above the threshold at which symptoms improve (e.g., with phenylephrine) may be beneficial (Rordorf et al., 2001; Hillis et al., 2003).

Antiplatelets and Anticoagulants in the Treatment of Acute Ischemic Stroke

All patients with acute ischemic stroke who do not receive tPA should receive aspirin within 48 hours. In patients who receive tPA, aspirin is generally initiated 24 hours after this if there has been no tPA-related hemorrhage. The IST and CAST trials demonstrated that aspirin administration within the first 48 hours after acute ischemic stroke reduced the risk of a second in-hospital stroke and increased survival to hospital discharge in spite of a small increased risk of intracerebral hemorrhage (IST trial, 1997; CAST trial, 1997; Chen et al., 2000). Aspirin is also an effective long-term secondary prevention medication (see “Antiplatelet Agents for Secondary Stroke Prevention”).

Although it was previously common practice to treat acute ischemic stroke patients with intravenous heparin, the IST trial suggested that risks of this treatment outweigh the benefits. The only situation in which acute anticoagulation is supported by data and guidelines at time of stroke is when stroke is due to venous sinus thrombosis (see “Cerebral Venous Sinus Thrombosis and Cortical Vein Thrombosis”). Other scenarios in which practitioners may treat acute ischemic stroke with anticoagulation are listed below, but it should be noted that many of these uses of anticoagulation for acute stroke are debated by practitioners and in the literature:

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  Acute basilar artery thrombosis

  
  
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  Artery-to-artery embolism from carotid stenosis while awaiting carotid endarterectomy (there are some data to support this from a subgroup analysis from the TOAST trial [Adams et al., 1999]).

  
  
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  Acute cervical artery dissection (carotid or vertebral); however, a large meta-analysis (Kennedy et al., 2012) and a single small randomized controlled trial (CADISS trial, 2015) suggest that there is no difference in outcome between patients treated with antiplatelets vs anticoagulation (see “Secondary Stroke Prevention in Patients With Cervical Artery Dissection” below).

  
  
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  Cardioembolism from atrial fibrillation, especially if the stroke occurs in a patient with known atrial fibrillation who has been off anticoagulation (e.g., for a minor surgical procedure) or is subtherapeutically anticoagulated. However, the risks and benefits of anticoagulation in the acute setting remain unclear. A delay in initiating (or resuming) anticoagulation is often considered if the stroke is moderate in size or larger, given that the daily risk of ischemic stroke from atrial fibrillation is felt to be less than the daily risk of hemorrhagic conversion of the stroke (The daily stroke risk in a patient with atrial fibrillation is roughly equivalent to the yearly stroke risk associated with the patient’s CHADS2 score divided by 365). Note that guidelines for anticoagulation for long-term secondary stroke prevention in atrial fibrillation are clear (see “Anticoagulation for Secondary Stroke Prevention” below).

Surgical Interventions in the Treatment of Acute Ischemic Stroke

In patients with large strokes of the cerebellum or large MCA strokes, stroke-related cerebral edema can raise intracranial pressure, which puts the patient at risk for herniation. In addition to hyperosmolar therapy (see “Hyperosmolar Therapy in the Treatment of Acutely Elevated Intracranial Pressure” in Chapter 25), surgery to decompress the edematous brain may be considered. For patients with large cerebellar strokes, suboccipital craniectomy is often performed and can lead to dramatic improvement. For patients with large MCA strokes, decompressive hemicraniectomy (removal of a skull flap on the side of the stroke to accommodate the swollen hemisphere) within 48 hours after stroke onset can be lifesaving and may improve outcomes (DECIMAL trial, 2007; DESTINY trial 2007; HAMLET trial, 2009; DESTINY II, 2014). However, many patients will have their lives saved only to survive with significant disability (see Ropper, 2014 for a cleverly titled editorial on the subject, “Hemicraniectomy: To Halve or Halve Not”). Therefore, decisions about whether to pursue this measure in patients with large MCA strokes must be individualized.

Supportive management measures for patients with ischemic stroke are discussed at the beginning of the chapter (see “Overview of Ischemic Stroke and Intracerebral Hemorrhage” above).

Evaluation for Etiology of Ischemic Stroke

Since the etiology of stroke most commonly involves either the intracranial vasculature, cervical vasculature, heart, and/or the effects of common atherosclerotic risk factors on these structures, the initial evaluation for stroke etiology assesses each of these:

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  The patient should be screened for modifiable risk factors: hypertension, diabetes (by serum glucose or hemoglobin A1c), hyperlipidemia (by serum lipids), smoking, and/or excessive alcohol use.

  
  
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  The intracranial and cervical vasculature can be assessed by MRA, CTA, or digital subtraction angiography. Time of flight MRA (which uses a measure of blood flow rather than contrast) may exaggerate the degree of stenosis compared to CTA or carotid ultrasound (since decreased flow may give the impression of decreased lumen caliber). If MRA and CTA are not available (or contraindicated), the carotid arteries can be assessed with Doppler ultrasound to look for stenosis or dissection.

  
  
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  The heart should be evaluated by transthoracic echocardiogram to evaluate for thrombus, left atrial dilatation (which may be associated with atrial fibrillation), and valvular vegetation (although transesophageal echocardiogram is more sensitive to assess for vegetation). Cardiac monitoring should also be performed to look for atrial fibrillation. If atrial fibrillation is not observed with in-hospital monitoring and there is not another clear etiology of stroke, prolonged cardiac monitoring (30 days) should be performed.

If the etiology of the stroke remains unclear after the above evaluation (cryptogenic stroke) or stroke occurs in a young patient, an expanded stroke evaluation is often undertaken. This may include:

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  Repeat prolonged cardiac monitoring to look for paroxysmal atrial fibrillation.

  
  
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  Agitated saline (bubble) study during the echocardiogram to look for patent foramen ovale (PFO). If a PFO is found, a search for deep venous thrombosis is undertaken with Doppler ultrasound of the lower extremities and MR venography (MRV) of the pelvis to evaluate for thrombosis of the pelvic veins (which may be caused by May-Thurner syndrome: Iliac vein thrombosis due to compression of the left common iliac vein by the right common iliac artery).

  
  
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  Evaluation for a hypercoagulable state: antiphospholipid antibodies (anti–cardiolipin antibodies, lupus anticoagulant, beta-2 glycoprotein antibody) and genetic mutations (protein C or S deficiency, antithrombin III deficiency, factor V Leiden, prothrombin gene mutation). Of these, only the antiphospholipid antibodies are associated with both arterial and venous thromboembolism. The others are primarily associated with venous thromboembolism, and so could only potentially cause a stroke if a PFO or other shunt between the venous and arterial circulations is present.

  
  
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  Screen for malignancy by positron emission tomography (PET) scan or CT chest/abdomen/pelvis since malignancy can lead to a hypercoagulable state.

  
  
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  Lumbar puncture to look for signs of an inflammatory or infectious etiology if vasculopathy is suggested on vascular imaging (e.g., primary central nervous system [CNS] vasculitis, secondary vasculitis due to infection such as varicella zoster virus).

  
  
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  Transesophageal echocardiogram to look for infectious, inflammatory, or neoplastic valvular lesions, atrial clot, or aortic atherosclerosis.

  
  
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  Blood cultures if there is concern for infectious endocarditis.

In spite of the many potentially exotic causes of stroke in the young, the most common causes remain the mundane ones: vascular risk factors, arrhythmia, and cervical artery dissection.

Secondary Prevention of Ischemic Stroke

Primary stroke prevention refers to modification of risk factors to prevent a first stroke. Secondary stroke prevention refers to modifying risk factors after stroke or TIA to reduce the risk of a subsequent stroke. Stroke secondary prevention measures include the following: