C h a p t e r 3 7
Disorders of Brain Function
933
stroke are family history of ischemic stroke, hyperten-
sion, cigarette smoking, overweight and obesity, high
blood cholesterol and other lipids, diabetes mellitus,
disorders of cardiac rhythm (e.g., atrial fibrillation), and
chronic kidney disease
21
(Table 37-4). The incidence of
stroke increases with age, and varies by sex and ethnic-
ity. Men have higher rates in the younger age groups,
though women catch up after menopause and live lon-
ger, resulting in higher rates of death among women.
African Americans have almost twice the risk of first-ever
strokes as whites. Blood pressure is a powerful determi-
nant of stroke risk. Individuals with a blood pressure
less than 120/80 mm Hg have about half the lifetime
risk of stroke compared with persons with hyperten-
sion. Heart disease, particularly atrial fibrillation and
other conditions that predispose to clot formation on
the wall of the heart or valve leaflets, or to paradoxical
embolism through right-to-left shunting, predisposes to
cardioembolic stroke. Polycythemia, sickle cell disease
(during sickle cell crisis), and blood disorders predispose
to clot formation in the cerebral vessels.
Other, less well-documented risk factors include obe-
sity, physical inactivity, alcohol and drug abuse, hyper-
coagulability disorders, hormone replacement therapy,
and oral contraceptive use. Clinical trial data indicate
that estrogen plus progestin, as well as estrogen alone,
increase stroke risk in postmenopausal, generally healthy
women, and provide no protection for women with
established heart disease. Although extensively used in
the past, the use of hormone therapy is no longer recom-
mended (see Chapter 40). Heavy alcohol consumption
can lead to hypertension, hypercoagulability of blood,
reduction of cerebral blood flow, and greater likeli-
hood of atrial fibrillation. Cocaine use causes both isch-
emic and hemorrhagic strokes by inducing vasospasm,
enhanced platelet activity, and increased blood pressure,
heart rate, body temperature, and metabolic rate.
22
Classification.
Various methods have been used to clas-
sify ischemic cerebrovascular disease. A common clas-
sification system identifies the five main mechanisms
of stroke as stroke subtypes and their frequency: 20%
large artery atherosclerotic disease (both thrombosis
and arterial emboli); 25% small vessel or penetrating
artery disease (so-called lacunar stroke); 20% cardio-
genic embolism; 30% cryptogenic stroke (undetermined
cause); and 5% other causes (i.e., migraine, vessel dissec-
tion, coagulopathy).
7
Ischemic Penumbra in Evolving Stroke.
During the
evolution of a stroke, there usually is a central core of
dead or dying cells, surrounded by an ischemic band or
area of minimally perfused cells called the
penumbra
(“halo”). Brain cells of the penumbra receive marginal
blood flow, and their metabolic activities are impaired.
Although the area undergoes an “electrical failure,” the
structural integrity of the brain cells is maintained.
4,23
Reversal of the penumbral injury depends on the suc-
cessful and timely return of adequate circulation, the
volume of toxic products released by the neighboring
dying cells, the degree of cerebral edema, and alterations
in local blood flow. If the toxic products result in addi-
tional death of cells in the penumbra, the core of dead
or dying tissue enlarges, and the volume of surrounding
ischemic tissue increases.
Transient Ischemic Attacks.
Transient ischemic attacks
(TIAs) are brief episodes of neurologic dysfunction result-
ing from focal cerebral ischemia not associated with
infarction.
18,24–26
A TIA or “ministroke” is equivalent
to “brain angina” and reflects a temporary disturbance
in cerebral blood flow, which reverses before infarction
occurs, analogous to angina in relation to heart attack.
The traditional definition of TIAs as a neurologic deficit
resolving within 24 hours was developed before the mech-
anisms of ischemic cell damage and the penumbra were
known and before the newer, more advanced methods of
neuroimaging became available. A more accurate defini-
tion now is a transient deficit without time limits, best
described as a zone of penumbra without central infarc-
tion.
20
The causes of TIAs are the same as those of isch-
emic stroke and include atherosclerotic disease of cerebral
vessels and emboli. Transient ischemic attacks are impor-
tant because they may provide warning of impending
stroke. In fact, the risk for stroke is 15% in the 3 months
following a TIA.
20
Diagnosis of TIA before a stroke may
permit surgical or medical intervention that prevents an
eventual stroke and associated neurologic deficits.
Large Vessel (Thrombotic) Stroke.
Thrombi are the
most common cause of ischemic strokes, usually occur-
ring in atherosclerotic blood vessels.
1,4
In the cerebral
circulation, atherosclerotic plaques are most commonly
found at arterial bifurcations of large arteries. Common
sites of plaque formation include the origins of the inter-
nal carotid and vertebral arteries, and junctions of the
basilar and vertebral arteries. Cerebral infarction can
result from an acute local thrombosis and occlusion
at the site of chronic atherosclerosis, with or without
embolization of the plaque material distally, or from
critical perfusion failure distal to a stenosis (water-
shed). These infarcts often affect the cortex, causing
aphasia or hemineglect, visual field defects, or transient
TABLE 37-4
Modifiable and Unmodifiable Risk
Factors for Stroke
Modifiable Factors
Unmodifiable Factors
• Hypertension
• Age
• Hyperlipidemia
• Gender
• Smoking
• Race
• Diabetes
• Heredity
• Heart disease
Atrial fibrillation
Wall motion defects
• Carotid artery disease
• Coagulation disorders
• Obesity/inactivity
• Heavy alcohol use
• Cocaine use
