Chapter 19: Vascular Diseases of the Brain and Spinal Cord

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

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

• Intracranial or spinal hemorrhage at five possible sites:

  • Epidural hematoma: between the skull or spine and dura

  • Subdural hematoma: between the dura and arachnoid

  • Subarachnoid hemorrhage: between the arachnoid and brain or spinal cord

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

  • Intraventricular hemorrhage (within the ventricular system of the brain)

• Cerebral venous sinus thrombosis

• Vascular malformations

• 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:

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

• Evaluation of swallowing and prevention of aspiration.

• Control of blood glucose to avoid hypoglycemia or hyperglycemia.

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

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

• Evaluation for and management of elevated intracranial pressure.

• Early mobilization.

• 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.

• 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):

• Age: 1 point if ≥60

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

• Clinical symptoms of TIA

  • 2 points for unilateral weakness or

  • 1 point for speech disturbance without weakness or

  • 0 points for any other symptoms without weakness or speech disturbance

• Diabetes: 1 point if present

• 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:

• The arteries:

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

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

• The heart: cardiac monitoring and echocardiogram

• 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:

• Atherosclerosis and thromboembolic disease of the arteries

• Lipohyalinosis of small penetrating arteries (small vessel disease)

• Carotid or vertebral artery dissection

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

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

• 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:

• Local irritation of the blood vessels by subarachnoid hemorrhage or meningitis

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

• 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:

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

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

• Moyamoya (which can be primary or secondary)

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

• 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:

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

• Cardiac valvular disease (and mechanical cardiac valves)

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

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

• Infective endocarditis with septic embolization

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

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

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

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

• 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.

• 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:

• 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)

• Sickle cell anemia

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

• 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:

• Acute basilar artery thrombosis

• 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]).

• 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).

• 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:

• 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.

• 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.

• 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:

• Repeat prolonged cardiac monitoring to look for paroxysmal atrial fibrillation.

• 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).

• 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.

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

• 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).

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

• 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:

• Hyperlipidemia should be controlled by diet, exercise, and statin therapy.

• Hypertension should be controlled by diet, exercise, and if necessary, antihypertensive medications.

• Blood sugar in diabetics should be controlled by diet, exercise and if necessary, medications.

• Patients should be aided in quitting smoking and reducing excessive alcohol intake.

• Patients should be on an antiplatelet agent (unless they require anticoagulation; see “Antiplatelet Agents for Secondary Stroke Prevention” and “Anticoagulation for Secondary Stroke Prevention” below).

• Patients with atrial fibrillation should be anticoagulated with warfarin or a novel oral anticoagulant (apixaban, rivaroxaban, dabigatran) unless there is a contraindication to anticoagulation, in which case an antiplatelet agent may be used.

• Patients with symptomatic moderate or severe carotid stenosis should be considered for intervention with carotid endarterectomy or carotid artery stenting (see “Secondary Stroke Prevention in Patients With Carotid Artery Stenosis” below).

• Patients with hypercoagulable states may require anticoagulation.

Antiplatelet Agents for Secondary Stroke Prevention

An antiplatelet agent is indicated for secondary ischemic stroke prevention in all patients who have had a TIA or ischemic stroke unless they are already receiving antithrombotic therapy with anticoagulation. The choices are aspirin, clopidogrel, and dipyridamole. Whether or not the dose of aspirin matters is debated; some practitioners believe that some patients may require higher doses of aspirin than other patients for adequate platelet inhibition. A number of studies have compared antiplatelet agents alone and in combination. The combination of dipyridamole and aspirin may be more effective for secondary stroke prevention than aspirin alone (EPSP2 trial, 1996; ESPRIT trial, 2006), but the side effect of headache, expense compared to aspirin, and twice daily dosing have led to dipyridamole/aspirin being less commonly used than aspirin alone.

Aspirin and clopidogrel together are not more effective than either alone in long-term secondary stroke prevention, and bleeding risk is increased compared to either alone (MATCH trial, 2004; CHARISMA trial, 2006; SPS3 trial, 2012). However, use of aspirin and clopidogrel together may have some benefit when used in the short term for the first 3 weeks following TIA or small ischemic stroke (CHANCE trial, 2013), although the study population in the CHANCE trial was exclusively Asian, so generalizability to non-Asian populations remains uncertain and is under investigation. The other scenario in which some practitioners utilize dual antiplatelet therapy for secondary stroke prevention is in symptomatic intracranial stenosis based on results from the medical management group in the SAMMPRIS trial (2014) (see “Secondary Stroke Prevention in Patients With Intracranial Arterial Stenosis” below).

In patients who have a TIA or stroke while already on an antiplatelet agent, some practitioners change from one antiplatelet to another or change the antiplatelet dose, although there are no data to guide such decisions.

One review of the complex array of data on antiplatelet agents for secondary stroke prevention sums up the topic with a tongue-in-cheek haiku expressing that being on an antiplatelet agent is most important, but that it may matter less which one(s): “For stroke prevention, / use an antiplatelet drug. / Treat hypertension” (Kent and Thaler, 2008).

Anticoagulation for Secondary Stroke Prevention

If atrial fibrillation is diagnosed, anticoagulation with warfarin or a novel oral anticoagulant (apixaban, rivaroxaban, dabigatran) is indicated for secondary stroke prevention unless there is a strong contraindication; in such patients an antiplatelet agent is used. Although anticoagulation for long-term secondary prevention has been studied in a variety of other scenarios such as noncardioembolic stroke (WARSS trial, 2001) and intracranial arterial stenosis (WASID trial, 2005), no benefit has been seen and increased risk of hemorrhage has been observed. Other scenarios aside from atrial fibrillation in which anticoagulation for secondary ischemic stroke prevention is often utilized include:

• Hypercoagulable states, whether genetic (e.g., protein C or S deficiency, antithrombin III deficiency, factor V Leiden, prothrombin gene mutation) or acquired (e.g., antiphospholipid antibodies, hypercoagulability of malignancy)

• Low cardiac ejection fraction due to cardiomyopathy. The WARCEF trial of warfarin vs. aspirin in patients with low ejection fraction found that the benefit of anticoagulation for primary stroke prevention was outweighed by the risk of major hemorrhage (driven primarily by GI hemorrhage with no difference in intracranial hemorrhage; WARCEF trial, 2012). However, anticoagulation may be considered for secondary stroke prevention after a stroke occurs in a patient with a low ejection fraction.

• Left ventricular thrombus.

• Stroke due to venous sinus thrombosis (see “Cerebral Venous Sinus Thrombosis and Cortical Vein Thrombosis” below).

Many practitioners advocate waiting 2–4 weeks from the time of an ischemic stroke before initiating anticoagulation if the size of the stroke is moderate or large to decrease the risk of hemorrhagic conversion of the ischemic stroke.

Secondary Stroke Prevention in Patients With Carotid Artery Stenosis

Carotid stenosis may be treated by carotid endarterectomy or carotid artery stenting to prevent further stroke in certain circumstances. Carotid stenosis is considered to be symptomatic if the stenosis is found ipsilateral to a stroke or a TIA in the anterior cerebral artery (ACA) territory or middle cerebral artery (MCA) territory (or posterior cerebral artery [PCA] territory if there is a fetal PCA; see “Arterial Supply of the Cerebral Hemispheres” in Chapter 7). If carotid stenosis is severe (70%–99%) and symptomatic, carotid intervention reduces the risk of subsequent stroke sufficiently to warrant the risks of intervention. With moderate (50%–69%) symptomatic stenosis, the initial trials showed a benefit of carotid intervention in men but not women, although the benefit was less than for severe stenosis. However, given advances in risk factor modification since these trials were performed, management of symptomatic moderate carotid stenosis is now debated. Mild symptomatic stenosis (<50%) and carotid occlusion are not considered indications for intervention (NASCET trial, 1991; VACS trial, 1991; ECST trial, 1998; Rothwell et al., 2003).

If carotid stenosis is discovered incidentally with no prior stroke or TIA referable to that carotid, it is considered to be asymptomatic. Intervention is not recommended for mild or moderate asymptomatic stenosis. Although there may be benefit to intervening in asymptomatic severe stenosis for primary stroke prevention, clinical trials addressing this (VACS trial, 1993; ACAS trial 1995; ACST trial, 2004) were performed before the advent of modern medical management (including statins), so the benefit of intervention in this scenario is now debated. Some practitioners recommend intervention for asymptomatic carotid stenosis >80%, but evaluate patients with asymptomatic stenosis <80% with serial ultrasounds and recommend intervention only if there is progression of stenosis or the patient has a stroke or TIA (making the carotid symptomatic). Another scenario in which an asymptomatic severe carotid stenosis may be intervened upon is in a patient undergoing cardiac surgery to reduce the risk of perioperative stroke, although this is also debated.

The choice between carotid endarterectomy and stenting depends on patient-specific characteristics: endarterectomy may be preferred for older patients, and stenting for younger patients (CREST trial, 2010). In patients in whom surgical risk is high (e.g., severe cardiac disease), stenting is often preferred.

Secondary Stroke Prevention in Patients With Symptomatic Intracranial Arterial Stenosis

Although procedural intervention can be effective in patients with symptomatic extracranial arterial disease, severe symptomatic intracranial arterial stenosis does not appear to improve with procedural intervention. The SAMMPRIS trial demonstrated that aggressive medical management (including statins and dual antiplatelet therapy with aspirin and clopidogrel) was superior to MCA stenting for secondary stroke prevention in patients with symptomatic MCA stenosis (SAMMPRIS trial, 2014). Therefore, some practitioners utilize dual antiplatelet therapy in patients with stroke or TIA due to intracranial arterial stenosis based on the results in the medical management group in this study.

The WASID trial demonstrated that there was no benefit—and increased risk—of anticoagulation for intracranial stenosis as compared to antiplatelet therapy (WASID trial, 2005).

Secondary Stroke Prevention in Patients With Patent Foramen Ovale

In about 25% of the population, the foramen ovale that connects the right and left atria in the fetal circulation fails to close after birth, leaving a patent foramen ovale (PFO). Through this conduit from the venous circulation to the arterial circulation, a venous clot can pass to the left heart and cause cerebral embolism (paradoxical embolus). A classic clinical history for paradoxical embolism is a stroke that occurs after the Valsalva maneuver (e.g., straining during a bowel movement), since the Valsalva maneuver increases right to left cardiac flow if a PFO is present.

In patients with stroke of unknown etiology (cryptogenic stroke), there is a higher prevalence of PFO. Therefore, in patients with cryptogenic stroke, evaluation for a PFO with agitated saline (bubble) study during the echocardiogram should be considered. If a PFO is found, the patient should be evaluated for a source of paradoxical embolism. The main sites to evaluate for deep venous thrombosis are the legs (with Doppler ultrasound) and the pelvis (with MRV). If a venous clot is discovered, anticoagulation is utilized and a search for a cause of hypercoagulability is pursued. If no clot is discovered in a patient with PFO and stroke, an antiplatelet agent is generally used for secondary stroke prevention. The question of whether a PFO should be percutaneously closed in patients with stroke remains unresolved after three clinical trials (CLOSURE 1 trial, 2012; Kitsios et al., 2013; PC trial, 2013; RESPECT trial, 2013) and is the subject of ongoing debate.

Secondary Stroke Prevention in Patients With Cervical Artery Dissection

For secondary stroke prevention in patients with stroke or TIA due to cervical artery dissection, antiplatelet agents and anticoagulation appear to be equivalent in large meta-analyses (Kennedy et al., 2012) and one small clinical trial (CADISS trial, 2015), although appropriate therapy has been debated. Stroke recurrence risk after dissection-related stroke is low (1%–2% over the first 3–6 months), making it challenging to perform an adequately powered trial. Most retrospective data are for carotid dissection with very limited data for vertebral artery dissection. Some practitioners avoid anticoagulation if a dissection extends intracranially due to risk of subarachnoid hemorrhage if an intracranial dissection were to rupture. Others argue that if there is no subarachnoid hemorrhage at the time of diagnosis of dissection, it is unlikely to occur and so anticoagulation may be safe (Metso et al., 2007). Treatment is generally maintained for 3–6 months with follow-up imaging to assess for recanalization or persistent occlusion of the vessel. Patients who are anticoagulated are generally switched to an antiplatelet agent after an initial period of anticoagulation.

There are no data to guide appropriate primary preventive management of patients who develop cervical artery dissection and present with local symptoms (e.g., neck pain, Horner’s syndrome, cranial nerve 9–12 palsies), but have not yet had a stroke or TIA. Some studies suggest that the risk of stroke in these patients in the acute setting is quite high (Biousse et al., 1995), leading some practitioners to use anticoagulation as primary prevention in the acute period if a cervical artery dissection is diagnosed in a patient with local symptoms only (i.e., no stroke or TIA), although others utilize antiplatelet agents.

A dissecting aneurysm (pseudoaneurysm) may develop in a dissected vessel over time, but this finding generally does not have any clinical significance with respect to outcome.

Rarer Causes of Ischemic Stroke: Vasculopathies, Vasculitis, and Genetic Disorders

Moyamoya

Moyamoya is the Japanese term for “puff of smoke,” which refers to the angiographic appearance of a “cloud” of collateral vessels that develop in response to stenosis of the distal internal carotid artery, proximal MCA, and/or proximal ACA unilaterally or bilaterally. Moyamoya disease refers to an idiopathic (presumed genetic) etiology that usually presents in childhood, whereas moyamoya syndrome denotes that moyamoya physiology has developed in response to another cause of vessel occlusion (e.g., prior radiation treatment, infectious or inflammatory vasculitis, sickle cell disease, atherosclerosis) or an associated underlying condition (e.g., Down’s syndrome or a neurocutaneous syndrome such as neurofibromatosis). Patients can present with TIA, ischemic stroke, or hemorrhage. TIA may be provoked by exertion or hyperventilation, possibly due to a “steal” phenomenon from the stenosed vessel and its collateral network. Diagnosis is made by angiography (CTA, MRA, or digital subtraction angiography), which demonstrates characteristic vessel occlusion and the “puff of smoke” of the collateral network.

Treatment of moyamoya can include surgical procedures that directly or indirectly link the extracranial and intracranial circulations to bypass the stenotic vessel in order to increase blood flow to the affected hemisphere(s). Direct linkage of the extracranial and intracranial circulations can be achieved through extracranial-intracranial (EC-IC) bypass: the superficial temporal artery (a branch of the external carotid artery) is connected to the MCA. Indirect linkage of the extracranial and intracranial circulations can be achieved by placing the superficial temporal artery in contact with the dura mater to promote neovascularization (synangiosis).

Cerebral Vasculitis

CNS vasculitis can be primary (primary vasculitis/angiitis of the central nervous system) or secondary. Secondary CNS vasculitis can be due to infection (e.g., varicella zoster virus, Aspergillus, meningovascular syphilis, bacterial meningitis) or due to systemic vasculitis (e.g., granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis), Churg-Strauss syndrome (also known as eosinophilic granulomatosis with polyangiitis)). Giant cell arteritis (also known as temporal arteritis), which classically presents with headache, visual loss, scalp pain, and jaw claudication, can rarely present with vasculitis of the vertebral arteries leading to posterior circulation strokes.

Primary CNS vasculitis can only be diagnosed definitively by brain biopsy. The symptoms and laboratory features of primary CNS vasculitis are all nonspecific: headache, subacute cognitive decline, strokes, inflammatory cerebrospinal fluid (CSF), and/or any of a number of diverse (and also nonspecific) MRI findings (strokes, mass lesions, white matter hyperintensities, vessel irregularities, and/or contrast enhancing lesion[s]). Headache and inflammatory CSF are so common in the disorder that the diagnosis is unlikely if they are not present, but both findings of course have broad differential diagnoses.

Clinicians may latch onto a diagnosis of CNS vasculitis when vascular irregularities are observed on MRA, CTA, or conventional angiogram, but these radiologic abnormalities only indicate the presence of a vasculopathy, which has a differential diagnosis far broader than vasculitis (e.g., atherosclerosis, reversible cerebral vasoconstriction syndrome (RCVS)). Since treatment of primary CNS vasculitis requires cyclophosphamide, if this diagnosis is being considered, biopsy confirmation is essential to avoid unnecessary risks of this medication without a definitive diagnosis.

Susac Syndrome

Susac syndrome is an autoimmune vasculopathy characterized by the triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Lesions in the central corpus callosum are characteristic, but additional nonspecific white matter lesions are also common and may lead to misdiagnosis of multiple sclerosis. CSF is typically inflammatory. Patients may not present with all three elements of the triad, but will most often develop them within months of onset. In patients in whom the diagnosis is suspected but not all aspects of the triad are clinically present, laboratory testing (i.e., MRI, fluorescein angiogram, audiometry) may reveal subclinical evidence of other elements of the triad.

Anti-endothelial cell antibodies have been described in association with the disorder. Treatment is with immunomodulatory therapy. The disease may be monophasic or relapsing.

Intravascular Lymphoma

Intravascular large B-cell lymphoma is a rare lymphoma that develops within the lumens of small and medium blood vessels. It is a multisystem disorder, but the presenting features may be neurologic due to strokes caused by lymphomatous occlusion of cerebral blood vessels. These are most commonly small vessel subcortical strokes. Strokes may be clinically apparent as acute-onset deficits, or the accumulation of small subclinical subcortical strokes may lead to a presentation with subacute cognitive decline. Any level of the nervous system may be involved, including myelopathy and neuropathy concurrent with or independent of brain involvement. Diagnosis often requires biopsy of affected nervous system tissue, although biopsy of skin lesions (if there is skin involvement) or random skin biopsy may be diagnostic in some cases. Treatment is with combination chemotherapy including anti–B-cell therapy with rituximab.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CARASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited CNS vasculopathy that causes migraines, strokes, and progressive neuropsychiatric dysfunction leading to dementia. MRI in CADASIL demonstrates a subcortical leukoencephalopathy (confluent T2/FLAIR hyperintensity in the white matter) with characteristic extension into the white matter of the anterior temporal lobes (Fig. 19–8) (this region can also be similarly affected in myotonic dystrophy; see “Myotonic Dystrophy” in Chapter 30). Diagnosis of CADSIL is made by genetic testing (mutation of the NOTCH3 gene on chromosome 19) or skin biopsy to evaluate blood vessels in the skin. There is no definitively proven stroke-prevention strategy, although any coexisting vascular risk factors for stroke should be well controlled, and many patients are given aspirin.

A recessive and much less common form of the disorder (CARASIL) is caused by mutation in the HTRA1 gene on chromosome 10. It is similar in clinical and radiologic presentation to CADASIL, but affected patients additionally have premature alopecia and lumbar spondylosis.

Mitochondrial Encephalopathy With Lactic Acidosis and Strokelike Episodes (MELAS)

Patients with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) may present with transient neurologic stroke-like episodes, generally before age 40. On neuroimaging, the stroke-like episodes in MELAS cause signal changes that are typically isolated to the cortex and do not conform to individual vascular territories. Accumulation of cerebral damage due to stroke-like episodes leads to encephalopathy. Migraines and seizures are common. Patients typically have other features of mitochondrial disease including short stature, deafness, myopathy, and lactic acidosis. MELAS is associated with mitochondrial mutation A3243G. Acute strokelike episodes may resolve with administration of L-arginine, and prophylactic administration may reduce the frequency of stroke-like episodes (Koga et al., 2005).

Long-term Sequelae of Ischemic Stroke: Recrudescence, Seizures, and Cognitive Impairment

Recrudescence

Patients who have had a prior stroke may present with reemergence of resolved deficits or worsening of baseline deficits in the setting of infection or other systemic illness, a phenomenon known as recrudescence. Any patient with a prior stroke is at risk for another, and so recurrent stroke is the primary differential diagnosis in this setting. However, it would be somewhat unlikely to have a stroke in the exact same place with the exact same deficits as a prior stroke, so when patients present with worsening of prior deficits, they should be evaluated for an infection or metabolic abnormality that could be a cause of recrudescence.

Post-stroke Seizures

Prior stroke is a common cause of epilepsy in older adults. Seizures generally emerge about 6 months to 1 year after infarct and require treatment with antiepileptic medications to prevent recurrence. An acute precipitant of seizures should be sought (e.g., infection, electrolyte abnormality, new medication; see Table 18–1), though may not be present. Seizures at the time of presentation of an acute ischemic stroke are uncommon (though more common if the stroke is due to venous sinus thrombosis or cortical vein thrombosis), but are more common in the setting of acute intracerebral hemorrhage.

Post-stroke Cognitive Impairment

Cerebrovascular disease can affect cognition due to stroke(s) in regions such as the hippocampus, thalamus, or frontal lobe(s), and/or can cause progressive cognitive impairment due to accumulation of chronic subcortical ischemic disease (see “Vascular Dementia” in Chapter 23).

Intracerebral hemorrhage (ICH) presents with sudden-onset focal neurologic deficits, as does acute ischemic stroke. Compared to ischemic stroke, however ICH is more often accompanied by one or more of the following clinical features (Runchey and McGee, 2010):

• Headache

• Nausea/vomiting

• Depressed level of consciousness at onset (due to displacement of brain tissue by the hematoma and/or intraventricular extension of hemorrhage)

• Extreme hypertension (diastolic pressure >110 mm Hg)

• Seizures at presentation

Any of these findings can also occur in the setting of ischemic stroke, and so definitive diagnosis requires CT. On CT, acute blood is hyperdense and visible at presentation (Fig. 19–9); this is in contrast to acute ischemic stroke, in which CT scan may be normal at presentation (see “Neuroimaging in Acute Ischemic Stroke” above). Vascular imaging (e.g., CTA or MRA) should be performed to assess for a vascular malformation that may require surgical intervention. If one or more spots of contrast is seen in the hematoma (spot sign), this is associated with a higher risk of hematoma expansion (Goldstein et al., 2007) (Fig. 19–10).

Acute Management of Intracerebral Hemorrhage

ICH expansion occurs most commonly in the first 24 hours, and within that period, most commonly within the first 6 hours. Acute management of ICH is geared toward prevention of hematoma expansion by lowering the blood pressure and reversing any coagulopathy if present (e.g., warfarin should be reversed with vitamin K and administration of fresh frozen plasma or prothrombin complex concentrate; heparin should be reversed with protamine). The degree to which blood pressure should be lowered remains unclear: it appears to be safe to lower systolic blood pressure as low as 140 mm Hg (INTERACT2 trial, 2013), but it remains uncertain whether lowering blood pressure that much improves outcomes as opposed to only lowering systolic blood pressure to less than 180 mm Hg. Intravenous antihypertensive infusion (typically with nicardipine) guided by intra-arterial blood pressure monitoring is often necessary.

Patients with acute ICH must be monitored closely in an intensive care unit setting with CT scan repeated for any change in neurologic examination. CT scans are typically repeated 6 hours after the initial scan and then at 24 hours to look for any evolution in the ICH. Electoencephalography (EEG) should be considered to evaluate for nonconvulsive seizures in patients whose examination appears to be worse than would be expected for the location and/or extent of hemorrhage, although thalamic and intraventricular hemorrhages can lead to fluctuations in level of consciousness without causing seizures.

In patients with large cerebellar ICH (>3 cm), surgical evacuation of the hematoma can be lifesaving. Although supratentorial hematoma evacuation does not appear to improve overall outcomes, it may be considered in patients with ICH close to the cortical surface (STICH trial, 2005; STICH 2 trial, 2013) or ICH that expands with rapid clinical deterioration in patients with a reasonable chance of recovery.

General supportive measures for ICH are discussed in the beginning of the chapter (see “Overview of Ischemic Stroke and Intracerebral Hemorrhage” above), and are similar to those for ischemic stroke, except that pharmacologic DVT prophylaxis is generally not initiated until 24–48 hours after ICH (pneumatic compression stockings should be utilized until that point).

Etiologies of Intracerebral Hemorrhage

The causes of ICH include:

• Chronic hypertension. Hypertensive hemorrhage has a predilection for the deep brain structures (basal ganglia, thalamus, and deep subcortical white matter), the anterior pons, and the cerebellum. These are sites of perforating vessels that appear particularly susceptible to damage due to chronic hypertension. Lobar hemorrhage may also be caused by hypertension.

• Cerebral amyloid angiopathy (CAA): CAA-related hemorrhages are most commonly lobar (see “Cerebral Amyloid Angiopathy” below).

• Head trauma.

• Coagulopathy (inherited, acquired, or due to anticoagulant use) or thrombocytopenia (e.g., disseminated intravascular coagulation [DIC], thrombotic thrombocytopenia purpura [TTP], acute leukemia).

• Rupture of a vascular malformation (e.g., aneurysm, arteriovenous malformation, cavernous malformation).

• Hemorrhage into an ischemic stroke (hemorrhagic conversion), which is more common with embolic strokes, septic emboli in endocarditis, and stroke in the PCA territory.

• Cerebral venous sinus thrombosis (see “Cerebral Venous Sinus Thrombosis and Cortical Vein Thrombosis” below).

• Cocaine (due to acute hypertension).

• Hemorrhagic cerebral metastases. The metastatic tumors reported to be most susceptible to hemorrhage are melanoma, renal cell carcinoma, thyroid cancer, and choriocarcinoma. However, since lung metastases are far more common than any of these, the most common hemorrhagic brain metastases are due to lung cancer. Since acute blood may make the radiologic detection of an underlying mass difficult, contrast-enhanced CT or MRI may be repeated several months after ICH if there is suspicion for an underlying mass.

Cerebral Amyloid Angiopathy

The same amyloid protein that accumulates in the brain in Alzheimer’s disease can accumulate in cerebral blood vessels, a condition known as cerebral amyloid angiopathy (CAA). CAA may coexist with Alzheimer’s disease, but the two can occur independently. Like Alzheimer’s, CAA is predominantly a disease of the elderly. Amyloid deposition in blood vessels leads to increased risk of intracerebral hemorrhage. CAA-related ICH is most commonly juxtacortical lobar hemorrhage (as compared to the deep hemorrhages that occur with hypertension). In CAA-related ICH, additional asymptomatic lobar microhemorrhages are often noted on gradient echo (GRE) and susceptibility-weighted (SWI) MRI sequences with a predilection for the gray–white junction of the occipital lobes (Fig. 19–11). Convexal subarachnoid hemorrhage (i.e., in the sulci) can also occur, leading to superficial siderosis (see “Superficial Siderosis” below). Risk of CAA-related hemorrhage is increased in patients with the ε4 and ε2 alleles of the APOE gene.

Although the diagnosis of CAA is often made when elderly patients have a lobar ICH, some patients may present with amyloid spells. These spells are transient episodes of focal sensory or motor deficits believed to be related to microhemorrhages. Amyloid spells should be considered in the differential diagnosis for TIA and seizure in older patients, especially if the MRI demonstrates microhemorrhages suggestive of CAA.

The diagnosis of CAA should be considered in patients over age 55 with lobar ICH without another clear cause of ICH (considered “possible CAA”), and is especially likely in that setting if there are additional lobar microhemorrhages limited to the cortex/juxtacortical regions on GRE/SWI sequences (considered “probable CAA”; definite diagnosis requires histologic diagnosis) (Knudsen et al., 2001). Patients with ICH due to CAA are at high risk for recurrent ICH. Some practitioners recommend avoidance of anticoagulation in such patients (though a patient with CAA-related ICH and a mechanical valve may be an exception to this recommendation), and recommend using antiplatelets only if there is a strong indication (Eckman et al., 2003)

A rare variant of CAA is CAA-related inflammation. In this condition, patients present with subacute cognitive decline and/or seizure, and imaging reveals asymmetric inflammatory lesions (T2/FLAIR hyperintensities) and multiple microhemorrhages (Fig. 19–12). Cerebrospinal fluid may be inflammatory and marked clinical improvement with steroids may be observed. The clinical course may be monophasic, relapsing, or progressive.

Resuming Anticoagulation After Anticoagulation-Associated Intracerebral Hemorrhage

In patients with anticoagulant-associated hemorrhage, the question often arises as to if and when to reinitiate anticoagulation. This is a scenario for which there are no randomized controlled trial data, and requires a careful balance of the perceived benefit of anticoagulation weighed against the perceived risk of anticoagulation. The highest risk scenario for being off of anticoagulation is in patients with a mechanical prosthetic cardiac valve in the mitral position, and so anticoagulation is often reinitiated within days after ICH in patients with mechanical valves.

Management of pulmonary embolism and other systemic thrombosis (e.g., DVT, limb ischemia) in patients with recent ICH depends on how long it has been since the ICH, the risk to the other organs of not anticoagulating (e.g., has pulmonary embolism led to right heart strain?), and whether other potential interventions for thrombosis aside from systemic anticoagulation could be performed (e.g., can inferior vena cava filter be placed in the case of DVT? Can a local procedure such as thrombectomy or local anticoagulant infusion be performed for limb ischemia?)

Although atrial fibrillation substantially elevates the risk for ischemic stroke, it has a relatively low daily risk of ischemic stroke (the percentage stroke risk per year associated with the patient’s CHADS2 score divided by 365). Therefore, after an ICH in a patient with atrial fibrillation, anticoagulation is often held for several weeks. With respect to the risks of anticoagulation from the ICH perspective, one decision analysis suggests that the risk of ICH recurrence after lobar CAA-related hemorrhage with anticoagulation outweighs the benefits of stroke prevention in the setting of atrial fibrillation, whereas the risk of ICH recurrence after deep/hypertensive hemorrhage may be outweighed by the benefit of anticoagulation in patients with a high risk of recurrent ischemic stroke (i.e., high CHADS2 score) (Eckman et al., 2003).

All such decisions must take each individual patient’s clinical scenario into account from both the ICH perspective (i.e., lobar vs deep, time since ICH) and the thrombosis perspective (i.e., differing risks of not anticoagulating in the setting of mechanical valve, DVT, pulmonary embolism, atrial fibrillation).

CNS vascular malformations are abnormal collections of blood vessels that can present with hemorrhage, seizure, and/or focal deficits, or may be discovered incidentally if neuroimaging is obtained for another indication. Diagnosis of the type of vascular malformation can often be made by radiologic characteristics (Table 19–3, Figs. 19–13, 19–14, 19–15). In patients with ICH without a clear etiology (i.e., not clearly due to hypertension, anticoagulant use, probable CAA) and no clear vascular lesion on CTA or MRA, digital subtraction angiography should be performed to evaluate for a vascular malformation.

Arteriovenous malformations (AVMs) are the vascular malformations most likely to cause ICH and are the best studied with respect to the risk of ICH. Risk factors for hemorrhage due to an AVM include prior ICH, deep location, and deep venous drainage. Treatment can include surgical excision or radiation therapy when symptomatic or thought to be at high risk for hemorrhage.

Subarachnoid hemorrhage (SAH) can be caused by:

• Aneurysm rupture or bleeding from other types of vascular malformations

• Head trauma

• Venous sinus thrombosis or cortical vein thrombosis

• Reversible cerebral vasoconstriction syndrome (RCVS)

• Cerebral amyloid angiopathy (CAA)

SAH in one or a few adjacent sulci (convexal SAH) is suggestive of trauma, cortical vein thrombosis, reversible cerebral vasoconstriction syndrome (RCVS), or CAA as an etiology (Fig. 19–16A).

SAH in the basal cisterns and/or more widely distributed is concerning for aneurysm rupture unless there is a clear history of trauma (Fig. 19–16B).

Aneurysmal Subarachnoid Hemorrhage

SAH due to rupture of an intracranial aneurysm leads to death in about half of patients, with a significant percentage dying before they reach the emergency room. Patients present with an acute-onset headache that is maximal at onset (thunderclap headache), classically the “worst of their life.” Headache can be isolated or may be accompanied by meningismus, nausea/vomiting, cranial nerve palsies, altered consciousness (from confusion to coma), and/or seizures. Some patients report a prior severe “sentinel headache” in the preceding weeks.

Diagnosis is generally made by noncontrast CT scan, which is extremely sensitive within the first day after symptom onset, but sensitivity decreases with time from the initial hemorrhage and with smaller hemorrhage volumes. If CT is negative and suspicion is high, lumbar puncture should be performed to evaluate for blood products. SAH must be differentiated from blood in the CSF due to traumatic lumbar puncture. CSF findings suggestive of SAH are the persistence of a similar quantity of red blood cells over several tubes and xanthochromia. Xanthochromia refers to a change in CSF color (most sensitively detected by spectrophotometry) signifying blood breakdown in the CSF, demonstrating that blood has been in the CSF for longer than the time of lumbar puncture. If suspicion for SAH remains high despite normal CT and normal or equivocal lumbar puncture results, angiography should be performed. If there is CT or lumbar puncture evidence of SAH but angiography is unrevealing, angiography is generally repeated after 1–2 weeks. Although the sensitivity of CTA continues to improve, digital subtraction angiography remains the gold standard for diagnosis of intracranial aneurysms.

Prevention and Management of Neurologic Complications of Subarachnoid Hemorrhage

Patients with aneurysmal SAH should be monitored in an ICU setting for complications of SAH due to ruptured aneurysm (Table 19–4). Neurologic complications include rebleeding, seizures, hydrocephalus (due to blockage of CSF flow by subarachnoid blood), vasospasm (due to irritation of the blood vessels by subarachnoid blood), and delayed cerebral ischemia.

Definitive treatment of a bleeding aneurysm to prevent rebleeding is with surgical clipping or endovascular therapy. If surgical intervention must be delayed for more than 2–3 days, aminocaproic acid may be administered in this period to reduce the risk of rebleeding. If the patient is on an antiplatelet or anticoagulant, this should be held and anticoagulants should be reversed as in patients with ICH. Until the aneurysm is secured, blood pressure should be controlled to reduce rebleeding risk, but the precise blood pressure goal has not been clearly established. After an aneurysm is secured, blood pressure is generally allowed to autoregulate to prevent hypoperfusion and/or vasospasm.

If seizures occur in the setting of SAH, they should of course be treated. Some practitioners administer prophylactic antiepileptics to prevent seizures, although this practice is debated in patients who have not had seizures.

If hydrocephalus is present, an external ventricular drain (EVD) is usually placed.

Vasospasm usually occurs between 3 days and 1 week after SAH. Nimodipine (a calcium channel blocker) is administered to prevent vasospasm. Vasospasm may manifest as new focal deficits, and can be screened for by transcranial Doppler ultrasound (TCD). TCD may reveal decreased flow velocity due to vasospastic arterial narrowing before clinical signs of ischemia appear. Vasospasm can be treated by increased intravascular volume repletion and vasopressors. If these measures are inadequate, catheter-based therapies (balloon angioplasty or intra-arterial vasodilators) may be indicated.

Non-neurologic complications of SAH include hyponatremia (due to syndrome of inappropriate secretion of antidiuretic hormone [SIADH] and/or cerebral salt wasting), cardiac arrhythmias, heart failure, and neurogenic pulmonary edema. Cardiopulmonary complications of SAH are likely due to the sympathetic surge induced by cerebral injury. Supportive measures include maintenance of euglycemia, euthermia, and euvolemia, as well as prevention of DVT. For DVT prophlyaxis, mechanical prophylaxis is generally utilized until 24 hours after securing of the aneurysm, after which prophylactic anticoagulation may be used.

Perimesencephalic Subarachnoid Hemorrhage

SAH restricted to the cisterns immediately surrounding the brainstem (predominantly the interpeduncular and prepontine cisterns) is only rarely associated with aneurysm (less than 10% of cases) and has a far more benign prognosis compared to aneurysmal SAH (Fig. 19–17). If this pattern of SAH is found, patients generally still undergo angiography to look for aneurysm.

Unruptured Intracranial Aneurysms

Screening for intracranial aneurysms in asymptomatic patients is generally only undertaken in patients with two or more first-degree relatives with aneurysms, but is sometimes also considered in patients with a genetic predisposition to aneurysms (e.g., polycystic kidney disease, Ehlers-Danlos syndrome). Such patients are generally screened every 5 years with MRA or CTA.

With increasing use of MRI/MRA, incidental aneurysms are identified with increasing frequency. Risk of rupture is lowest with aneurysms <7 mm, and treatment of aneurysm carries substantial perioperative risk, so small incidental aneurysms are generally followed with serial imaging at 6 months and then yearly to evaluate for any growth. If growth is seen, intervention may be considered. Smoking, hypertension, and use of cocaine can all increase risk of rupture, so these modifiable risk factors must be addressed if present.

In patients with unruptured aneurysms, the question often arises as to whether antiplatelets and anticoagulants are safe. Although these medications are unlikely to increase the risk of rupture, if rupture were to occur, resulting SAH could be worsened. In general, aspirin is considered safe, but anticoagulation requires a careful assessment of the risks and benefits of use in each individual patient. For example, accepting the risk of the use of anticoagulants may be unavoidable with a mechanical heart valve or large pulmonary embolism, but risk stratification by CHADS2 score in patients with atrial fibrillation may lead to a more complex analysis of risk and benefit depending on the size and location of the aneurysm.

Intraventricular hemorrhage (IVH) can occur as a complication of ICH or SAH, or it can occur in isolation (Fig. 19–18). The differential diagnosis for the etiology of IVH is similar to ICH and SAH: coagulopathy, trauma, bleeding from a vascular malformation or aneurysm, and extension from ICH. Due to blockage of CSF flow, IVH typically presents with symptoms of elevated intracranial pressure: headache, nausea/vomiting, and altered level of consciousness. Blood pressure should be controlled and coagulopathy reversed if present, just as in ICH. Placement of an extraventricular drain (EVD) is often necessary due to development of hydrocephalus. Some patients may ultimately need ventriculoperitoneal shunting for persistent impaired CSF resorption due to blood in the ventricular system. The use of intraventricular administration of tPA to lyse intraventricular clot is under investigation.

Subdural hematoma (SDH) occurs due to tearing of bridging veins that run between the brain and the dura. Head trauma is the most common cause of acute SDH. In older adults with brain atrophy (leading to greater tension on the bridging veins) or in patients on anticoagulation, the trauma necessary to cause SDH may be so minor that it cannot be recalled by the patient.

Unlike most cerebrovascular conditions that develop suddenly, SDH may also develop more insidiously (chronic SDH) after minor trauma (e.g., in patients who are elderly and/or on anticoagulation) or in the setting of intracranial hypotension (see “Decreased Intracranial Pressure (Intracranial Hypotension)” in Chapter 25). Chronic SDH can present with subacute headache, alterations in consciousness, focal deficits, and/or seizures. Some patients have fluctuating symptoms found ultimately to be due to seizures by EEG monitoring, but in some patients, these fluctuations have no electrographic correlate and may be due to fluctuations in mass effect from the SDH.

Acute SDH appears as a crescent-shaped hyperdensity on CT (blood filling the space between the dura and the brain) (Fig. 19–19A). With chronic SDH, there may be different radiographic densities in the subdural space due to blood products of varying ages. Chronic SDH can develop into a hygroma, a fluid collection without obvious blood products in the subdural space.

The decision of whether to surgically drain an acute traumatic SDH depends on the size of the SDH and the degree of resultant midline shift, as well as the clinical state of the patient (Glasgow Coma Scale [GCS] and pupil symmetry). Pupillary asymmetry or a decline in GCS by 2 or more points from the time of trauma to the time of evaluation in a patient with SDH are generally indications for surgery no matter what the size of the SDH. An acute SDH of 10 mm or more or with 5 mm or more of SDH-induced midline shift is generally considered an indication for surgical drainage irrespective of neurologic examination findings. Size of SDH and clinical state are also used to determine candidates for surgical drainage in patients with chronic SDH.

Epidural hematoma (EDH) is almost always caused by head trauma. Normally, the dura is fixed to the skull with no true epidural “space.” This is in contrast to the subdural space, which is a true space between the brain and the dura. Head trauma leading to damage to the middle meningeal artery is the most common etiology of EDH. As arterial blood accumulates, it “dissects” the dura away from the skull, leading to a lens-shaped collection of blood on neuroimaging (Fig. 19–19B). It may be this pathophysiology that accounts for the “lucid interval” between head trauma and decline in consciousness that occurs in some patients with EDH: The arterial blood must reach a certain volume/pressure to overcome the adherence of the dura to the skull, and when it does, the hematoma rapidly expands, raising intracranial pressure. However, this lucid interval is not always present in patients with EDH.

Similar to SDH, size of the EDH and clinical state determine which patients require urgent operative drainage. Surgical evacuation is generally necessary for EDH >30 mL regardless of clinical state, or EDH with coma (GCS <9) or pupil asymmetry.

Venous sinus thrombosis (VST) should be considered in patients with unexplained progressive headache, especially if symptoms or signs of elevated intracranial pressure are present (e.g., nausea, vomiting, headache worse when supine, papilledema, sixth nerve palsy/palsies [see “Symptoms and Signs of Increased Intracranial Pressure” in Chapter 25]), although patients may present with isolated headache. Patients may also present with seizures, ischemic stroke, ICH, or SAH.

Diagnosis of VST is made definitively by demonstrating venous occlusion on dedicated venous imaging (MRV or CTV; Fig. 19–20), but should be suspected on nonvascular noncontrast CT or MRI in the following scenarios:

• Diffuse cerebral edema without trauma

• ICH that is parasagittal (caused by thrombosis of the superior sagittal sinus), bithalamic (caused by thrombosis of the internal cerebral veins), temporo-occipital (caused by transverse sinus thrombosis), or juxtacortical (caused by cortical vein thrombosis)

• ICH with edema out of proportion to the size of the hemorrhage

• Convexal SAH (i.e., in the cerebral convexities; also called sulcal SAH)

• Thrombosed cortical vein (hyperdensity on CT or clot seen on GRE/SWI MRI sequences)

• Hyperdensity over one of the sinuses on noncontrast CT (cord sign)

• Lack of flow in the posterior superior sagittal sinus on contrast-enhanced CT (empty delta sign)

MRV and CTV can reveal thrombosed venous sinuses, but irregularity of the sinuses due to normal structures can be misleading (e.g., arachnoid granulations, asymmetries due to unilateral transverse sinus hypoplasia). When in doubt, contrast-enhanced MRI can be used to look for filling defects in the venous sinuses.

VST can be caused by CNS or sinus infection, or any etiology of a hypercoagulable state including:

• Oral contraceptive use

• Pregnancy/peripartum period

• Systemic malignancy

• Systemic inflammatory disease (e.g., inflammatory bowel disease, lupus)

• Genetic hypercoagulable state (factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency)

• Antiphospholipid antibody syndrome

• Nephrotic syndrome

• Dehydration

Treatment is with anticoagulation. Anticoagulation is thought to be safe and effective even if there is ICH secondary to VST. If patients worsen in spite of anticoagulation, endovascular interventions can be considered, although data are limited. In cases of extensive thrombosis with elevated intracranial pressure, management of intracranial pressure is required (see “Treatment of Acutely Elevated Intracranial Pressure” in Chapter 25).

An evaluation for a hypercoagulable state should be undertaken in all patients with VST unless there is another clear ongoing underlying trigger (e.g., malignancy) that would warrant life-long anticoagulation whether a specific hypercoagulable abnormality is found or not. It should be noted that some of the components of the hypercoagulable evaluation can be abnormal in the setting of anticoagulation and/or thrombosis, confounding interpretation when evaluated in the acute setting. For example, protein C and protein S are lowered by warfarin; antithrombin III is lowered by heparin.

If an ongoing irreversible hypercoagulable state is discovered during evaluation, life-long anticoagulation may be necessary (e.g., active malignancy, clotting disorder). This is generally not necessary for provoked VST (e.g., peripartum, dehydration, trauma, CNS/sinus infection), for which anticoagulation is usually maintained for 3–6 months.

Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) is a condition named for the most common and most prominent location of radiographic changes (posterior), usual clinical course (reversible), and one of the component clinical features (encephalopathy). However, the radiographic changes may extend beyond the posterior of the brain; the syndrome can include seizures, headache, and/or visual changes with or independent of encephalopathy; and in rare cases the disorder can result in ischemia or hemorrhage resulting in irreversible disability. The classic syndrome is one in which a patient develops headache, seizure, visual changes, and/or altered mental status with characteristic neuroimaging changes consisting of subcortical T2/FLAIR white matter hyperintensities in the occipital lobes in the MCA-PCA borderzone territories (see “Watershed (Borderzone) Territories” in Chapter 7) that resolve when the underlying cause is treated (Fig. 19–21). Etiologies of PRES include:

• Hypertensive emergency

• Eclampsia

• Immunosuppressive agents (e.g., tacrolimus, cyclosporine)

• Chemotherapeutic agents (e.g., bortezomib)

There is a broad spectrum of neuroimaging changes in this condition beyond the classic appearance described above, including contrast enhancement, vascular narrowing on MRA or CTA, cerebral ischemia/hemorrhage, and/or signal changes in the anterior circulation (a common pattern is in the MCA-ACA watershed/borderzone territories; see “Watershed (Borderzone) Territories” in Chapter 7), brainstem, cerebellum, and/or gray matter (cortex and/or deep gray).

Treatment is of the underlying cause: lowering blood pressure in hypertensive emergency; magnesium, lowering blood pressure, and delivery of the baby in eclampsia; and removal of the offending agent in medication-induced PRES. If seizures are present and persistent, these should be treated with antiepileptic medications, but if the cause is identified and treated, prolonged antiepileptic therapy is generally not necessary beyond a short course while the underlying cause is treated.

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

Reversible cerebral vasoconstriction syndrome (RCVS) (also called Call-Fleming syndrome) is a condition of reversible vasospasm of the intracranial arteries, as the name suggests. Patients most commonly present with isolated thunderclap headache (sudden-onset, maximal-at-onset), although focal features and/or seizures may be seen if the condition causes ischemic stroke or hemorrhage. When intracranial hemorrhage occurs, it is most commonly convexal SAH (see Fig. 19–16A). Vasospasm is apparent on vascular imaging, which has the appearance of alternating constriction and dilation of vessels in a “sausage-link”–like (or “beaded”) appearance (Fig. 19–22). The most common causes of RCVS include:

• Drugs: marijuana, cocaine, amphetamines

• Medications: selective serotonin reuptake inhibitors (SSRIs) and over-the-counter cold medicines with sympathomimetics (e.g., pseudoephedrine)

• Postpartum period (postpartum angiopathy), which can occur with or without preeclampsia/eclampsia

• PRES: the two conditions may co-occur

Treatment involves discontinuation of the underlying drug or medication trigger if one is identified. Some practitioners treat RCVS with nimodipine, verapamil, and/or magnesium. Most patients recover completely both clinically and radiologically within days to weeks after symptom onset.

Superficial Siderosis

Superficial siderosis refers to chronic subarachnoid bleeding leading to deposition of blood products around the brainstem, cranial nerves, and cerebellum. The classic symptoms are insidious development of hearing loss (due to involvement of cranial nerve 8), ataxia (due to cerebellar involvement), and motor dysfunction with upper motor neuron signs (due to involvement of the descending corticospinal tracts). MRI reveals low T2 signal surrounding the circumference of the brainstem and cerebellum with evidence of blood surrounding these structures on SWI/GRE sequences. Causes include prior head or spine trauma, arteriovenous malformation, and CNS tumors, although, in many cases, no clear cause is determined. Although CAA can cause siderosis, it does not typically cause the classic clinical features of superficial siderosis. Although some practitioners consider treatment of superficial siderosis with iron chelators, this is often ineffective.

Many of the same types of vascular pathology that occur in the brain can also occur in the spinal cord, although much less commonly. This includes ischemic stroke, epidural hematoma, spinal cord hemorrhage, and vascular malformations.

Ischemic Stroke of the Spinal Cord

Ischemic stroke of the spinal cord presents with sudden-onset myelopathy. The main differential diagnosis is acute spinal cord compression, and urgent imaging is needed to evaluate for the latter since surgical intervention is often necessary in acute cord compression. Spinal cord infarction most commonly occurs in the setting of aortic disease (rupture of abdominal aortic aneurysm or complication of surgical repair of abdominal aortic aneurysm). A rarer etiology of spinal cord infarction is fibrocartilaginous embolism, in which disc fragments are thought to embolize to the spinal vasculature after trauma or exertion. Fibrocartilaginous embolism typically presents with acute back pain in addition to myelopathy.

The spinal cord is supplied by the anterior spinal artery and paired posterior spinal arteries (all of which originate from the vertebral arteries). The anterior spinal artery is fed by radicular arteries that branch from the aorta along the length of the spinal cord. The largest radicular branch and one of the most vulnerable to damage in abdominal aortic surgery is the artery of Adamkiewicz, normally found at the level of the lower thoracic spine (at about T10). The anterior spinal circulation is vulnerable to disruption, which most commonly occurs due to aortic pathology or aortic surgery. Anterior spinal artery territory infarction typically presents as bilateral lower extremity weakness and loss of pain and temperature sensation with preserved proprioception and vibration sense (see “Anterior Cord Syndrome” in Chapter 5). There is also a watershed territory between the anterior and posterior circulations in the central cord, and central cord infarction can occur with global hypoperfusion.

MRI with diffusion-weighted imaging (DWI) sequences may demonstrate spinal cord infarction, but DWI is not as sensitive in the spinal cord as it is for cerebral infarction. Given the rarity of spinal cord infarction, appropriate treatment is not well established. Based on the pathophysiology, perfusion should be maintained by avoiding hypotension, and some practitioners utilize lumbar CSF drainage to enhance spinal cord perfusion.

Spinal Hemorrhage

Hemorrhage into the spinal cord (hematomyelia) or its surroundings (epidural, subdural, subarachnoid) can be caused by spinal trauma, anticoagulation, or bleeding from a spinal vascular malformation. The most common compartment for spinal hemorrhage is the epidural space. A spinal epidural hematoma can result from trauma or as a complication of spinal surgery or epidural administration of anesthesia. Epidural hematoma is generally easily identified on CT as a hyperdensity in the spinal canal. Treatment is surgical evacuation.

Spinal Dural Arteriovenous Fistula

The most common arteriovenous (AV) malformation of the spine is the spinal dural AV fistula (AVF), which typically presents with a progressive myelopathy that may fluctuate over time spontaneously and/or with exertion. Spinal dural AVF most commonly occurs in older men. MRI typically reveals diffuse spinal cord edema and prominent posterior flow voids (Fig. 19–23), and the malformation itself may sometimes be visualized with MRA. The myelopathy may worsen if steroids are administered, which may occur if the initial clinical impression is that cord edema seen on MRI represents transverse myelitis rather than venous congestion from an AVF. Definitive diagnosis requires spinal angiogram, and treatment may be surgical or catheter based. Spinal dural AVF is an important underrecognized and treatable cause of progressive myelopathy.