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C H A P T E R 145

STROKE

Emer McGrath, Michelle Canavan, and Martin O’Donnell

Stroke is the leading cause of acquired adult disability worldwide and incidence of stroke in high-income countries, compared with a more
the fourth most common cause of death in developed countries. than 100% increase in the incidence of stroke in middle- and low-
Primary stroke subtypes include ischemic stroke, intracerebral hemor- income countries.
rhage (ICH), and subarachnoid hemorrhage (SAH). Each stroke
subtype has differing etiologies, outcomes, and management strate-
gies. The past 20 years has seen considerable advances in diagnosis Traditional Risk Factors for Stroke
(emergence of widely available neuroimaging) and treatment of acute
stroke. In addition, there is an increased awareness of the importance Both ischemic stroke and ICH are associated with a number of
of covert stroke (stroke on neuroimaging without a history of acute potentially modifiable risk factors, including hypertension, diabetes
clinical stroke). In this chapter we provide an overview of stroke, with mellitus, smoking, poor diet, and physical inactivity. The INTER-
a primary focus on ischemic stroke, which is the most common cause STROKE study, which included 26,919 participants from 32
of stroke worldwide. countries, reported that 10 key risk factors are associated with 90%
of the population-attributable risk (PAR) of ischemic stroke, namely
hypertension, smoking, waist-to-hip ratio, diet, physical activity level,
DEFINITION diabetes mellitus, alcohol intake, psychosocial stress/depression,
cardiac causes such as atrial fibrillation, and ratio of apolipoprotein
Stroke is defined by the World Health Organization (WHO) as B to apolipoprotein A1 (Table 145.1). Of these risk factors, five were
“rapidly developing clinical signs of focal (at times global) disturbance associated with about 80% of the PAR for all stroke (hypertension,
of cerebral function, lasting more than 24 hours or leading to death smoking, abdominal obesity, physical inactivity, and diet), and each
with no apparent cause other than that of vascular origin.” This defi- was an important risk factor for both ischemic and hemorrhagic
nition is conventionally considered to include ischemic stroke, ICH, stroke. Thus a large proportion of stroke is potentially preventable
and SAH. However, because of advances in our knowledge about the through population-based interventions aimed at modifying these
nature, timing, and clinical presentation of stroke and its mimics, as risk factors. Hypertension is the strongest risk factor for both ischemic
well as significant advances in neuroimaging (particularly magnetic stroke and ICH and, arguably, the most modifiable though lifestyle
resonance imaging [MRI]), an updated definition of central nervous intervention (e.g., reducing salt intake) and use of antihypertensive
system (CNS) infarction has been proposed by the American Heart medications.
Association (AHA)/American Stroke Association (ASA). CNS infarc-
tion (including hemorrhagic infarction) is defined as “brain, spinal
cord, or retinal cell death attributable to ischemia, based on: (1) PATHOBIOLOGY
pathologic, imaging, or other objective evidence of cerebral, spinal
cord, or retinal focal ischemic injury in a defined vascular distribu- Stroke can be primarily classified into ischemic stroke (Fig. 145.1)
tion; or (2) clinical evidence of cerebral, spinal cord, or retinal focal and hemorrhagic stroke. Hemorrhagic stroke is further subtyped into
ischemic injury based on symptoms persisting ≥24 hours or until ICH (Fig. 145.2) and SAH. In North America and Europe, approxi-
death, and other etiologies have been excluded.” According to the mately 87% of strokes are caused by ischemia, with the remaining
AHA/ASA, a transient ischemic attack (TIA) is defined as a transient 13% occurring caused by hemorrhage.
episode of neurologic dysfunction caused by focal brain, spinal cord,
or retinal ischemia, without acute infarction.
Etiological Classification of Ischemic Stroke

EPIDEMIOLOGY Unlike acute coronary syndrome, which is primarily caused by large-
vessel atherosclerosis, the underlying mechanisms for ischemic stroke
Frequency are more heterogeneous. The most commonly used etiological clas-
sification is the Trial of Org 10172 in Acute Stroke Treatment
The WHO estimates that 15 million people suffer a stroke each year, (TOAST) classification system, which focuses on the pathophysiologic
and of these, 5 million people are left with permanent disability. In mechanism of ischemic stroke, based on clinical features and the
the absence of further effective population-based interventions, a results of diagnostic investigations (brain imaging, cardiac investiga-
projected 6.5 million stroke deaths will occur in 2015 and 7.8 million tions, and neurovascular imaging). The five etiological subcategories
deaths in 2030. A small decrease in age-specific stroke mortality rates in the TOAST classification system are: large-artery, cardioembolism,
has been projected from 2005 to 2030, which is largely because of a small-artery occlusion (or lacunar ischemic stroke), stroke of other
decline in mortality rates in high-income countries. However, because determined etiology, and stroke of undetermined etiology.
of an increasingly aging population worldwide, the crude stroke
mortality rates are projected to increase across all ages, from 89 per
100,000 in 2005 to an estimated 98 per 100,000 in 2030. The Large-Artery Stroke
increase in stroke mortality will be most marked in developing
countries, where increases in stroke incidence are most prominent. Large-artery stroke is usually a consequence of atherosclerosis in the
Worldwide, stroke shows significant geographical variation in terms extracranial (carotid or vertebral) and/or intracranial arteries (e.g.,
of incidence (and temporal trends), case fatality, and case mix (i.e., middle cerebral or basilar artery), with plaque rupture and thrombus
stroke subtypes). A systematic review of population-based studies formation. Ischemic stroke may result from artery-to-artery throm-
reported that from 1970 to 2008 there was a 42% decrease in the boembolism with distal occlusion or, less commonly, by acute

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