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Chapter 145 Stroke 2135

valvular vegetations in nonbacterial thrombotic endocarditis or infec- be classified as either primary or secondary, depending on the underly-
tive endocarditis. Mechanical mitral and aortic valves are associated ing cause. Primary ICH accounts for about 80%–90% of cases and is
with a sufficiently high risk for ischemic stroke that indefinite oral the result of spontaneous rupture of small intracerebral blood vessels,
anticoagulant therapy is indicated. Rheumatic heart disease still usually damaged by chronic hypertension (and other vascular risk
accounts for half of all cases of endocarditis in some regions of the factors) or amyloid angiopathy. Antithrombotic therapy, particularly
world (e.g., India and Africa). Several epidemiologic studies have anticoagulant therapy, is an important risk factor for ICH. Secondary
shown a link between ischemic stroke and Trypanosoma cruzi infec- ICH occurs as a result of vascular abnormalities (ruptured saccular
tion (Chagas disease) in South America. aneurysm, arteriovenous malformation), tumors (e.g., cavernous
angioma, intracerebral neoplasm), impaired coagulation (e.g., because
Postcardiac of use of oral anticoagulants or bleeding disorders such as hemophilia
Atherosclerotic plaques in the aortic arch, proximal to the left sub- or von Willebrand disease), hemorrhagic transformation of ischemic
clavian artery, can be postcardiac sources of emboli, either atheroma- stroke, septic emboli, vasculitis, moyamoya disease, and alcohol or
tous debris or platelet emboli, which then enter the cerebral circulation illicit drug use (e.g., cocaine, amphetamines).
resulting in an ischemic stroke. Severe aortic arch atheromas (>4 mm
in diameter) are associated with a fourfold increase in the risk of Subarachnoid Hemorrhage
ischemic stroke and peripheral embolism. Although anatomically a SAH refers to bleeding within the subarachnoid space, which is the
large vessel source, aortic arch disease is usually included in cardiac space between the arachnoid and pia mater. SAH accounts for about
causes of ischemic stroke because it is often identified via transesopha- 3%–5% of all strokes and is most commonly caused by rupture of
geal echocardiography. an intracranial aneurysm (approximately 80%–85% of cases). Idio-
pathic nonaneurysmal perimesencephalic hemorrhage accounts for
about 10% of cases, and the remaining 5% are caused by rare causes
Small-Vessel Disease such as inflammatory lesions of cerebral arteries (e.g., mycotic aneu-
rysm, polyarteritis nodosa, primary angiitis), noninflammatory
Approximately 20% of all ischemic strokes are caused by lacunar or lesions of intracerebral vessels (e.g., arterial dissection, cerebral
small-vessel infarcts. Lacunar infarcts are the result of occlusion of arteriovenous malformations, cerebral amyloid angiopathy, cerebral
small, deep-penetrating arteries, such as the lenticulostriate branches venous thrombosis, moyamoya disease), vascular lesions of the spinal
of the anterior cerebral and middle cerebral arteries. The terminal cord (e.g., saccular aneurysm of the spinal artery, spinal arteriovenous
pathophysiological mechanism underlying small-artery occlusion is malformation), coagulopathy (e.g., hemophilia, von Willebrand
believed to be local thrombosis secondary to microatheroma (lipid- disease), sickle cell disease, tumors (e.g., malignant glioma), trauma,
laden macrophages, cholesterol deposits, and subintimal fibroblast and drug use (cocaine, anticoagulants).
proliferation) and lipohyalinosis (the intermediate stage between
fibrinoid necrosis and microatheroma, which has characteristics of
both arterial atheromatous lipid deposits and arteriolar hyalinization Covert Stroke
disease). Growing evidence supports the concept that damage to the
glycocalyx, by factors such as hyperglycemia, hypertension, and Clinically overt stroke is considered to represent only a fraction of all
smoking, may contribute to vascular endothelial damage. Other episodes of cerebral infarction. The advent of contemporary MRI
causes of small-artery occlusion include microemboli from athero- sequences has identified a large burden of subclinical cerebrovascular
sclerotic plaques, polycythemia vera, antiphospholipid antibodies, disease, which includes covert infarction, white matter hyperintensi-
amyloid angiopathy, cerebral autosomal dominant arteriopathy with ties, cerebral atrophy, and microbleeds. Covert stroke is common; for
subcortical infarcts and leukoencephalopathy (CADASIL), cerebral example, a systematic review of eight population-based studies
autosomal recessive arteriopathy with subcortical infarcts and leuko- reported a prevalence of silent brain infarcts in an older population
encephalopathy (CARASIL), Sneddon syndrome, and various types of 8%–28%. Moreover, covert stroke has been associated with an
of small-vessel arteritis. The combination of mitochondrial myopathy, increased risk of cognitive decline, dementia, depression, and gait
encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is impairment (Box 145.1).
an inherited progressive disorder characterized by mitochondrial
dysfunction and early onset of stroke, typically before the age of 40
years. The mitochondrial angiopathy hypothesis suggests that the Hematologic Disorders and Ischemic Stroke
lesions are secondary to ischemia, which is caused by mitochondrial
and vascular dysfunction of cerebral small arteries. Inherited Thrombophilia
In general, studies have reported either no association or a modest
Ischemic Stroke of Other Determined Etiology association between inherited thrombophilia and ischemic stroke.

Cerebral Vein Thrombosis
Cerebral vein thrombosis accounts for less than 1% of ischemic
strokes, and typically affects younger people. The superior sagittal, BOX 145.1 What Is Cryptogenic Ischemic Stroke?
transverse, and cavernous sinuses are those most commonly affected
by thrombosis. Venous thrombosis results in localized edema and In some cases, the cause of stroke cannot be definitively determined
and the stroke is classified as “stroke of undetermined etiology.” A
venous infarction, which often becomes hemorrhagic, and may raise stroke may be classified in this category when one of the following two
intracranial pressure (ICP). Reported risk factors for cerebral vein conditions is met: (1) an extensive evaluation is negative, which
thrombosis include inherited thrombophilia; acquired prothrombotic includes large-vessel imaging, and complete cardiovascular assess-
states such as antiphospholipid syndrome, pregnancy, and the puer- ment is negative; or (2) the diagnostic evaluation is incomplete. The
perium; infections such as otitis, sinusitis, and mastoiditis; chronic most important determinant of the proportion of patients labeled as
inflammatory conditions such as Wegener granulomatosis and sar- having cryptogenic stroke is the extent of the etiological diagnostic
coidosis; trauma such as a head injury, dehydration, and injury to the testing, including transesophageal echocardiography. In studies that
jugular veins or sinuses during neurosurgical procedures. have completed an extensive etiological workup, the proportion of
patients designated as having cryptogenic stroke is small (5%–15%).
Intracerebral Hemorrhage In older patients with complete evaluation, paroxysmal atrial fibrillation
is suspected to be a common underlying cause of ischemic stroke in
ICH accounts for approximately 10%–15% of all strokes (a larger older adults with “cryptogenic” ischemic stroke.
proportion is reported in middle- and low-income countries), and can