stroke among women, ethnic groups, young adults, and children

Handbook of Clinical Neurology, Vol. 92 (3rd series)Stroke, Part IM. Fisher, Editor# 2009 Elsevier B.V. All rights reserved

Chapter 17

Stroke among women, ethnic groups,

young adults, and children

JONATHAN W. STURM1, MARK T. MACKAY2, AND AMANDA G. THRIFT3*

1Department of Neurology, Gosford Hospital, Central Coast Area Health, Gosford, Australia2Department of Neurology, Royal Children’s Hospital, Parkville, Australia

3Baker Heart Research Institute, Melbourne, Australia

There are a number of different groups of people among

whom the incidence and etiology of stroke differ. Inci-

dence is somewhat lower among women than men, and

is considerably lower among young adults and children.

There are some ethnic groups amongwhom the incidence

and the composition of the subtypes of stroke vary con-

siderably. Stroke in children is more commonly asso-

ciated with other disorders, such as non-atherosclerotic

arteriopathies and cardiac disorders.Among young adults

similar disorders are also associated with stroke; how-

ever, other factors such as recreational drug use and

migraine play a role, as well as the development of

atherosclerosis. In this chapter we will discuss the most

important differences among these groups.

17.1. Stroke in women

The incidence of stroke has consistently been shown to

be lower in women than in men (Sudlow and Warlow,

1997). In the majority of incidence studies, however,

the number of strokes occurring among women is

greater (Bamford et al., 1988; Ricci et al., 1991;

D’Alessandro et al., 1992; J�rgensen et al., 1992; Bonitaet al., 1993; Czlonkowska et al., 1994; Feigin et al.,

1995; Brown et al., 1996; Thrift et al., 2000). This

apparent disparity is due to the fact that stroke incidence

increases with age and there are more elderly women

than elderly men in the population.

There are many physiological differences between

women and men that predispose them to diseases in

different ways. For stroke these differences are largely

*Correspondence to: Dr Amanda G. Thrift, Head, Population Hea

Road, Melbourne, Victoria 8008, Australia. E-mail: Amanda.Th

1100.

attributed to childbearing, pregnancy, contraception,

and maintenance of hormone levels during and after

menopause. In addition, there is some evidence that

other risk and protective factors for women are not the

same as for men, and that some factors may require

higher exposures in one group than the other. For exam-

ple, in a cohort study in the USA, serum albumin con-

centrations of more than 4.4 g/dl have been shown to

be associated with reduced stroke risk among men aged

65–74 years but the same association has not been

observed among women (Gillum et al., 1994). Many

of these findings have either not been replicated by

others, are inconsistent, or the studies have low power,

and so these factors will not be discussed further.

17.1.1. Pregnancy

Women are at increased risk of stroke during pregnancy,

with approximately 11 ischemic strokes and nine intra-

cerebral hemorrhages being reported to occur with

every 100 000 deliveries in the 15–45-year age group

(Kittner et al., 1996). The incidence was lower in a study

conducted in France, being 4.3 per 100 000 deliveries for

non-hemorrhagic stroke and 4.6 per 100 000 deliveries

for intraparenchymal hemorrhage (Sharshar et al., 1995).

The reason for this lower incidence may partly be the

inclusion of a longer postpartum period in the former

study, with the majority of strokes occurring during this

period.

During pregnancy and the 6-week postpartum per-

iod combined Kittner and colleagues (1996) found that

lth Research, Baker Heart Research Institute, 75 Commercial

[email protected]; Tel: (613) 8532-1111; Fax: (613) 8532-

mailto:[email protected]

Current OCP use

Estrogen dose

Progesterone typeFirst generation

Second generation

Third generation

0.5 1.0

Relative Risk (95% CI)

10.0

High (>50µg)

Medium (50µg)

Low (<50µg)

Fig. 17.1. Summary of relative risk (and 95% confidence

intervals (CI)) of the oral contraceptive pill for ischemic

stroke. (Adapted from Gillum et al., 2000.)

RM

the relative risk (RR) for cerebral infarction was 1.6

(95% confidence interval (CI) 1.0–2.7), and for intra-

cerebral hemorrhage was 5.6 (95% CI 3.0–10.5). The

greatest risk of stroke occurred during the early post-

partum period, being 5.4 (95% CI 2.9–10.0) for

ischemic stroke and 18.2 (95% CI 8.7–38.1) for intra-

cerebral hemorrhage. In another investigation of the

role of pregnancy in ischemic stroke risk, no such

association was found (Nightingale and Farmer, 2004).

However, in this latter study there were only two preg-

nancies among the women with ischemic stroke and the

confidence intervals were wide (1.23, 95% CI 0.34–

4.41), encompassing the point estimate of the previous

investigation. Therefore it appears that there is an

increased risk of stroke among women during pregnancy

and in the early postpartum period.

In a recent case-control study conducted in the

USA, Brown and colleagues (2006) investigated the

association between a history of pre-eclampsia and

ischemic stroke risk. They found that women with a

history of pre-eclampsia more often had a non-

pregnancy-related ischemic stroke than women with-

out a history of this condition (odds ratio (OR) 1.63,

95% CI 1.02–2.62). Therefore, although the greatest

risk of stroke appears to be in the early postpartum

period, it may be that people with this condition con-

tinue to be at elevated risk of ischemic stroke beyond

the postpartum period.

There are a number of potential mechanisms for an

increased predisposition to stroke during pregnancy

and the early postpartum period, including athero-

sclerosis, cardioembolism, arterial dissection during

labor, hematological disorders, paradoxical embolism

from the venous system of the pelvis or legs, and fat,

air, or amniotic fluid embolism (Sharshar et al.,

1995; Jeng et al., 2004). In addition Sharshar and col-

leagues (1995) reported that eclampsia was associated

with 47% of pregnancy-related non-hemorrhagic

strokes and 44% of intraparenchymal hemorrhages in

the northern region of France. Thus, the association

between pregnancy and stroke is biologically plausible.

17.1.2. Oral contraceptive pill

There have been numerous investigations of the asso-

ciation between the oral contraceptive pill and stroke

since this possibility was first raised in 1962 (Lorentz,

1962). Evidence for an association has been conflict-

ing. In studies conducted in the 1960s and 1970s the

relative risk of stroke associated with the oral contra-

ceptive pill was reported to be between 3.14 and 8.80

(Sartwell et al., 1969; Vessey and Doll, 1969; Colla-

borative Group for the Study of Stroke in Young

338 J.W. STU

Women, 1973, 1975). Over the next few decades this

association diminished somewhat, with relative risk

estimates tending towards lower values of between 2

and 4 (Petitti et al., 1996; WHO Collaborative Study

of Cardiovascular Disease and Steroid Hormone Con-

traception, 1996a, b; Schwartz et al., 1997, 1998; Hei-

nemann et al., 1998; Lidegaard, 1999; Poulter et al.,

1999; Lidegaard and Kreiner, 2002).

The decline in the risk of stroke associated with the

oral contraceptive pill over the past few decades has

largely been attributed to its changing composition.

This is demonstrated by the results of a recent meta-

analysis (Gillum et al., 2000), where a dose–response

relationship between estrogen levels and ischemic

stroke risk was observed (Fig. 17.1). The relative risk

for ischemic stroke increased from 2.08 (95% CI

1.55–2.80) among those taking low dose estrogen oral

contraceptive pills (<50 mg) to 2.78 (95% CI 2.00–

3.85) among those taking medium doses (50 mg) and4.53 (95% CI 2.17–9.50) for those taking high

(�50 mg) doses (Gillum et al., 2000). Most modern

oral contraceptive pills contain 30–35 mg of estrogen

and so it is possible that the risk of stroke with the oral

contraceptive pill will decline further. Evidence for

this has been provided by the results of a recent Danish

case-control study that included 626 women with

ischemic stroke or transient ischemic attack (TIA)

(Lidegaard and Kreiner, 2002). In this study the rela-

tive risk of ischemic stroke or transient ischemic attack

was 1.6 (95% CI 1.3–2.0) among those taking oral

contraceptive pills with an estrogen dose of 30–

40 mg, which is somewhat lower than that reported

among those taking doses less than 50 mg in the recent

meta-analysis (Gillum et al., 2000).

Investigation of the effect of the progesterone

type of oral contraceptive pill on the risk of ischemic

stroke provides some conflicting results. In the large

ET AL.

OU

meta-analysis conducted by Gillum and colleagues

(2000) there was a non-significant decrease in risk of

ischemic stroke with third-generation preparations. A

similar decline with the newer preparations was

reported by Lidegaard and Kreiner (2002), where a

lower relative risk was found among those taking

third-generation preparations (OR 1.4; 95% CI 1.0–

1.9) than first-generation preparations (OR 4.5; 95%

CI 2.6–7.7). In contrast to this, Kemmeren and collea-

gues (2002) found no difference in the adjusted odds

ratio for ischemic stroke between the different prepara-

tions of progesterone. The reason for this disparity is

unclear, although it is possible that prescribing practices

may account for some of the observed differences. If the

newer preparations are seen as being safer and are pre-

scribed to higher-risk women in some areas, this might

potentially bias the results.

There have been few investigations of the risk of

either intracerebral hemorrhage or subarachnoid

hemorrhage among users of the oral contraceptive pill

(Hannaford et al., 1994; Thrift et al., 1996; Jick et al.,

1999). As shown in Table 17.1, these studies provide

evidence that the oral contraceptive pill does not infer

a greater risk of either intracerebral hemorrhage (Han-

naford et al., 1994; Thrift et al., 1996; Jick et al., 1999)

or subarachnoid hemorrhage (Hannaford et al., 1994).

Similar results have been reported from investigations

among a combined group of hemorrhagic strokes

(Collaborative Group for the Study of Stroke in Young

Women, 1975; Hirvonen and Idanpaan-Heikkila, 1990;

Petitti et al., 1996). This provides evidence that the oral

contraceptive pill does not appear to predispose to

either of the major hemorrhagic stroke subtypes.

Some investigators have reported that the risk of

stroke among oral contraceptive pill users is greater

among those who are hypertensive (Collaborative

Group for the Study of Stroke in Young Women,

1975), who smoke (Collaborative Group for the Study

of Stroke in Young Women, 1975; WHO Collaborative

Study of Cardiovascular Disease and Steroid Hormone

Contraception, 1996b; Heinemann et al., 1998), or who

suffer migraines (Collaborative Group for the Study

of Stroke in Young Women, 1975; Schwartz et al.,

1998; Bousser, 2004; Etminan et al., 2005). In contrast,

in their meta-analysis Gillum and colleagues (2000)

reported that oral contraceptive pill use appeared to

impart similar risks of ischemic stroke among smokers

and non-smokers, those with and without hypertension,

and those with and without migraine (Gillum et al.,

2000). Although this is reassuring, it is possible that

these additional risk factors are imbalanced between

groups because of prescribing practices. Such imbal-

ances may relate to the level of blood pressure or to

STROKE AMONG WOMEN, ETHNIC GR

the amount that women smoke. Therefore it might be

more prudent to avoid prescribing oral contraceptive

pills to women with these additional risk factors.

17.1.3. Hormone replacement therapy

A recently carefully conducted meta-analysis of nine

observational studies provided evidence for an increa-

sed risk of stroke among ever users of hormone replace-

ment therapy (RR 1.12; 95% CI 1.01–1.23) (Nelson

et al., 2002). The authors calculated that for every

10 000 postmenopausal women treated with hormone

replacement therapy per year there would be one extra

stroke among those aged 55–64 years, three extra strokes

among those aged 65–74 years, and six extra strokes

among those aged 75–84 years. Further analysis by stroke

subtype revealed that the increased risk of stroke was

largely attributable to an increased risk of ischemic stroke

(RR 1.20; 95% CI 1.01–1.40) (Nelson et al., 2002). In

contrast, there was no elevated risk of either subara-

chnoid haemorrhage (RR 0.80; 95% CI 0.57–1.04) or

intracerebral hemorrhage (RR 0.81; 95% CI 0.25–1.29).

Despite the fact that ischemic stroke was increased

among those taking hormone replacement therapy, the

authors of this meta-analysis suggested caution when

assessing the results (Nelson et al., 2002). This is

because women who take hormone replacement therapy

differ in ways that are known to decrease the risk of

cardiovascular disease. These women tend to be more

affluent, are leaner, have higher educational attainment,

exercise more often, and drink alcohol more regularly.

There have been three recent randomized trials of

hormone replacement therapy and stroke; two of these

were for secondary prevention of stroke (Simon et al.,

2001; Viscoli et al., 2001) while one was a primary

prevention study (Wassertheil-Smoller et al., 2003;

Anderson et al., 2004). In the secondary prevention

studies there was no evidence of a benefit or a detri-

mental effect of hormone replacement therapy on the

risk of stroke among either those with pre-existing cor-

onary heart disease (Simon et al., 2001) or those with a

prior ischemic stroke or transient ischemic attack

(Viscoli et al., 2001). There were two arms of the

Women’s Health Initiative, one involving the use of

estrogen plus progestin among postmenopausal

women aged 50–79 years (Wassertheil-Smoller et al.,

2003) and one on postmenopausal use of estrogen

among women aged 50–79 years with a prior hyster-

ectomy (Anderson et al., 2004). In the former of these

arms, a 31% increase in strokes was reported among

those taking estrogen plus progestin when compared

to placebo (Wassertheil-Smoller et al., 2003). This

was equivalent to about eight extra strokes for every

PS, YOUNG ADULTS, AND CHILDREN 339

Table 17.1

Summary of relative risk or odds ratio (and 95% confidence intervals (CI)) of the oral contraceptive pill for intracerebral hemorrhage

and subarachnoid hemorrhage

Location

Study

population Cases Controls

Oral contraceptive

pill status

Risk/odds ratio

(95% CI) Adjustments

Intracerebral hemorrhage

United Kingdom (Hannaford et al.,

1994)

GP database 22 66 Never user 1.0 Smoking and socioeconomic

status

Ever user 1.3 (0.5–3.8)

Current user 1.1 (0.2–7.1)

Former user 1.4 (0.5–4.2)

United Kingdom (Jick et al., 1999) GP database 29 116 Second generation

users

1.0 Nil

Use of desogestrel 1.2 (0.2–6.8)

Use of gestodene 1.4 (0.2–8.2)

Melbourne, Australia (Thrift et al.,

1996)

Cases-control

study

331 331 Ever used oral

contraceptive pills

0.89 (0.38–2.09) Hypertension, cholesterol,

previous cardiovascular

disease, exercise, body mass

index, smoking, and alcohol

consumption.

Subarachnoid hemorrhage

United Kingdom (Hannaford et al.,

1994)

GP database 73 219 Never user 1.0 Smoking and socioeconomic

status.Ever user 1.3 (0.7–2.5)

Current user 1.5 (0.6–3.7)

Former user 1.3 (0.7–2.5)

95% CI, 95% confidence interval.

OU

10 000 women-years of treatment. Moreover, when the

hazard ratios were adjusted for multiple comparisons

the confidence intervals crossed unity and so the asso-

ciation was no longer statistically significant (Nelson

et al., 2002; Patel et al., 2002). Similar results were

found for the use of estrogen therapy among postme-

nopausal women with a prior hysterectomy (Anderson

et al., 2004).

Although there is inconclusive evidence regarding

excessive stroke risk among postmenopausal women

taking hormone replacement therapy, there is now a

large body of evidence from meta-analysis and rando-

mized controlled trials that hormone replacement ther-

apy does not provide protection against ischemic

stroke (Simon et al., 2001; Viscoli et al., 2001; Nelson

et al., 2002; Wassertheil-Smoller et al., 2003; Ander-

son et al., 2004). Therefore there is no longer support

for the use of these agents in either the primary or

secondary prevention of ischemic stroke.

17.1.4. Summary

Women have a number of risk factors for stroke that are

unique. Many of these involve their reproductive capa-

city, although other factors may also be involved. An

increased risk of both ischemic stroke and intracerebral

hemorrhage has been observed during pregnancy, with

the highest risk occurring early in the postpartum per-

iod. There has been conflicting evidence for a role of

the oral contraceptive pill on ischemic stroke risk, which

appears to be mainly attributable to changing doses and

preparations over the decades. However, despite the fact

that there has been an amelioration of the risk of stroke

associated with use of the oral contraceptive pill with

the introduction of newer lower-dose preparations, a

significant risk persists. Similar conflicting evidence

was apparent for the use of hormone replacement ther-

apy in preventing stroke. However, with the publication

of a recent meta-analysis of observational studies as

well as the completion of several randomized controlled

trials, the evidence no longer supports a role for these

preparations in protecting against stroke and so these

drugs should not be prescribed for this purpose.

17.2. Ethnicity

17.2.1. Incidence and type of stroke

There have been a number of reports of differences in

subtypes of stroke between people of different ethnic

backgrounds. Early work conducted in Japan (Tanaka

et al., 1982; Ueda et al., 1988) demonstrated that hemor-

rhagic stroke comprised a larger proportion of strokes

(approximately 30%) than those occurring in European,


Australian, or American populations (15–20%) (Bam-

ford et al., 1990; Giroud et al., 1991; Ricci et al., 1991;

D’Alessandro et al., 1992; Tuomilehto et al., 1992;

Wolf et al., 1992; Anderson et al., 1993; Brown et al.,

1996). Intracerebral hemorrhages are also more com-

mon in China, with this subtype of stroke comprising

between 17% and 39% of strokes in different regions

(Zhang et al., 2003). In addition, there is some evidence

from hospital-based registries that hemorrhagic stroke

may account for between 26% and 46% of strokes in

South America (Saposnik et al., 2003). These are likely

to be overestimates, however, as hemorrhages usually

comprise the more severe strokes and are therefore more

likely to result in hospitalization.

In studies conducted in the USA and the UK the inci-

dence of stroke among blacks has been shown to be

approximately twice that of whites (Kittner et al., 1990;

Giles et al., 1995; Sacco et al., 1998; Stewart et al.,

1999; Kissela et al., 2004). Furthermore, the incidence

was greater among blacks for each of ischemic stroke,

intracerebral hemorrhage, and subarachnoid hemorrhage

(Stewart et al., 1999; Kissela et al., 2004). Similarly high

incidence rates were also observed among Hispanics

living in northern Manhattan (Sacco et al., 1998).

17.2.2. Risk factors

Differences in the incidence of stroke among different

ethnic groups have not been explained by differences

in social class, age, or sex (Stewart et al., 1999). How-

ever, there have been observed differences in other

risk factors. The prevalence of hypertension and dia-

betes was found to be greater among blacks than

whites in a multicenter study conducted in Europe,

while the prevalence of atrial fibrillation and smoking

was greater in whites (Hajat et al., 2004). In addition

to hypertension and diabetes, the prevalence of obesity

and inadequate physical activity was also greater

among blacks in a study conducted in the USA

(McGruder et al., 2004). In contrast, Hispanics had a

greater prevalence of diabetes than whites but a similar

prevalence of other risk factors (McGruder et al.,

2004). These differences in risk factors can be used

to guide community-based prevention strategies in dif-

ferent ethnic groups. Tailoring strategies toward those

risk factors that are particularly high in distinct ethnic

groups will ensure that prevention strategies are opti-

mized.

17.3. Stroke in young adults

A relatively small proportion of strokes occurs in

adults aged between 15 and 45 years. However, stroke

in young adults requires special consideration as the


RM

relative frequencies of underlying pathophysiological

mechanisms differ from those of the general stroke

population and because of the potential long-term

impact on independence and performance of familial,

occupational, and societal roles.

17.3.1. Incidence

In Western countries between 2% (Marini et al., 2001)

and 8% (Jacobs et al., 2002) of first-ever strokes occur

in people aged between 15 and 45 years, and in specia-

lized stroke centers the proportion may be as high as

12% (Bogousslavsky and Pierre, 1992). In developing

countries, 20–30% of strokes may occur in young

adults (Radhakrishan et al., 1986; Al Radjeh and

Awada, 2002). Annual incidence rates for first-ever

strokes at the age of less than 45 years are between

10 and 23 per 100 000 (Marini et al., 2001; Jacobs

et al., 2002). Even within the category of ‘young

stroke’, incidence increases with age, with only 30%

occurring in those aged less than 35 years (Marini

et al., 2001). Men have generally been found to have

greater incidence rates than women at all ages (Marini

et al., 2001; Jacobs et al., 2002); however, in those

aged less than 30 years a greater incidence has been

reported in women than men (Naess et al., 2002).

Similar to the general stroke population, incidence var-

ies among ethnic groups in people aged less than 45

years, with greater rates of stroke (Jacobs et al.,

2002) in blacks and Hispanics and greater rates of

transient ischemic attack (Kleindorfer et al., 2005) in

blacks than whites in the USA.

In population-based studies a higher proportion of

intracerebral hemorrhage and subarachnoid hemor-

rhage has been found in young adults compared to

342 J.W. STU

Table 17.2

Comparison of the etiology of ischemic stroke in children, yo

population

All stroke* (%)

Atherosclerosis 38–77

Nonatherosclerotic arteriopathy <3Cardioembolic 26–29

Atrial fibrillation} 70

Prothrombotic <1Illicit drugs <1

References:

*Yip et al., 1997; Petty et al., 1999; Grau et al., 2001.{Ruiz-Sandoval et al., 1999; Marini et al., 2001; Lee et al., 2002; Cer{deVeber et al., 1998; Chabrier et al., 2000; deVeber, 2000; Ganesan}Refers to proportion of those with a cardioembolic cause of stroke.

older stroke subjects (Marini et al., 2001; Jacobs

et al., 2002). In L’Aquila, Italy, of subjects aged 15–

45 years 22.1% had a subarachnoid hemorrhage,

20.9% intracerebral hemorrhage, and 57.0% ischemic

stroke. By contrast, in those aged more than 45 years

the proportions were 2.4% subarachnoid hemorrhage,

13.3% intracerebral hemorrhage, and 83.1% ischemic

stroke (Marini et al., 2001).

17.3.2. Etiology

The causes of stroke in young adults are similar to that

in the general stroke population but the relative fre-

quencies of those causes are different.

Aneurysms and arteriovenous malformations can be

identified as a cause of hemorrhagic stroke in young

adults in approximately 50% of cases (Ruiz-Sandoval

et al., 1999; Marini et al., 2001), hypertension in

approximately 13% (Ruiz-Sandoval et al., 1999), and

sympathomimetic drug use in 4–7% (Toffol et al.,

1987; Ruiz-Sandoval et al., 1999).

In the general stroke population the majority of

ischemic strokes are attributable to large-vessel athero-

thromboembolism and small-vessel disease, followed

by cardioembolism. However, in young adults the

proportion of ischemic stroke attributable to non-

atherosclerotic arteriopathies, cardioembolic mechan-

isms, prothrombotic states, and toxins is much greater

(Table 17.2).

17.3.2.1. Atherosclerosis

Atherosclerosis accounts for between 15% and 33%

of ischemic stroke in adults aged less than 45 years

(Blecic and Bogousslavsky, 1998; Cerrato et al.,

ET AL.

ung adults aged 15–44 years, and the general stroke

Young adults{ (%) Children{ (%)

15–33 <112–31 30–53

14–33 4–24

5–10 <11–8 18–38

5 <1

rato et al., 2004.

et al., 2003.

OU

2004; Varona et al., 2007), and in only 5% in those less

than 30 years (Bogousslavsky and Regli, 1987). Large-

vessel disease is more common in Western populations

(Adams et al., 1995), while small-vessel disease is

greater among blacks in the USA (Qureshi et al.,

1995) and among Taiwanese (Lee et al., 2002). By con-

trast, atherosclerosis accounts for between 38% and

77% of ischemic stroke in the general population

(large-artery and small-vessel disease combined; Yip

et al., 1997). Risk factors for atherosclerosis in young

adults are the same as in the general population:

hypertension, diabetes, smoking, and hyperlipidemia

(Cerrato et al., 2004).

17.3.2.2. Non-atherosclerotic arteriopathies

This heterogeneous group of disorders accounts for

12–31% of ischemic strokes in young adults (Blecic

and Bogousslavsky, 1998; Varona et al., 2007). This is

considerably greater than the proportion attributable to

these conditions in the general stroke population

(<3%; Petty et al., 1999; Grau et al., 2001). Carotid

and vertebral arterial dissection causes approximately

10% of strokes among those less than 40 years of age

and 20% among those less than 30 years of age (Guillon

et al., 1998). Dissection is usually spontaneous but can

be secondary to trauma, fibromuscular dysplasia, or

connective tissue disorders. A less common arteriopathy

is fibromuscular dysplasia, which occurs predominantly

in white women and usually involves the distal extracra-

nial vertebral and carotid arteries. Abnormalities in the

smooth muscle layer result in widening and narrowing

of the arterial lumen, leading to the characteristic ‘string

of beads’ appearance on angiography. Moyamoya dis-

ease (discussed in section 17.4.2.2; Fig. 17.2) often

causes childhood stroke but also accounts for between

1% and 6% of stroke in adults aged 15–45 (Bendixen

et al., 2001).

Cerebral autosomal dominant arteriopathy with sub-

cortical infarcts and leukoencephalopathy (CADASIL)


Fig. 17.2. Magnetic resonance angiogram of a patient with Moy

accounts for approximately 1% of ischemic strokes in

young adults (Williams et al., 1997). This genetic disor-

der is due to mutations in the Notch 3 gene on chromo-

some 19 (Chabriat et al., 1999). It is characterized by

recurrent subcortical ischemic strokes, with involve-

ment of the anterior temporal poles and external cap-

sules characteristically seen on magnetic resonance

imaging (MRI). Patients with this disorder usually

develop mood disturbance and dementia, and approxi-

mately 60% of patients also have a history of migraine.

Vasculitis is a relatively uncommon cause of stroke,

accounting for between 1% and 6% of strokes in

young patients in most series (Bendixen et al., 2001),

and rare among the general stroke population (<1%).

The diagnosis may be suspected following angio-

graphic evidence of long segmental or focal regions

of arterial narrowing, accompanied by single or multi-

ple infarctions or hemorrhages with or without lepto-

meningeal enhancement on MRI. However, a brain or

leptomeningeal biopsy is usually required for defini-

tive diagnosis. Central nervous system vasculitis

can be primary, or may occur secondarily to systemic

collagen vascular diseases, non-central-nervous-system

vasculitis, infections or toxins (Carolei and Sacco,

2003).

17.3.2.3. Cardioembolism

A cardioembolic cause for ischemic stroke is found in

14–33% of young adults (Bogousslavsky and Regli,

1987; Adams et al., 1995; Cerrato et al., 2004; Varona

et al., 2007), similar to the general stroke population

(Grau et al., 2001). Higher rates have been reported in

Persian young adults (Ghandehari and Moud, 2006).

Although atrial fibrillation is commonly associated with

cardioembolic stroke in older patients, it is an uncom-

mon cause in young adults with stroke (1–3%). Instead,

causes of cardioembolic stroke in young adults more

often include aseptic and infective endocarditis (intra-

venous drug users and those with prosthetic heart valves


amoya. Note the formation of extensive collateral vessels.

RM

are at high risk), left ventricular thrombus associated

with dilated cardiomyopathy or acute myocardial

infarction, and rarely atrial myxoma (Bendixen et al.,

2001; Cerrato et al., 2004). Another potential cause of

cardioembolic stroke is patent foramen ovale, which

appears to be a risk factor for ischemic stroke only in

those aged less than 55 years, not in older people (Over-

ell et al., 2000). Although patent foramen ovale is found

in approximately one-quarter of the normal population,

it is found at higher frequencies in people with crypto-

genic stroke. Whether a patent foramen ovale suspected

of causing a stroke should be closed is uncertain, as

there are no randomized clinical trials comparing medi-

cal therapy to surgical closure. In contrast to patent fora-

men ovale, evidence from recent studies suggests that

uncomplicated mitral valve prolapse is not a risk factor

for stroke (Orencia et al., 1995).

17.3.2.4. Prothrombotic states

Antiphospholipid antibodies (e.g., lupus anticoagulant,

anticardiolipin antibody) have been associated with

arterial thromboembolism and ischemic stroke (Asher-

son et al., 1989; Galli et al., 2003), accounting for a

small proportion (<1–8%) of stroke in young adults

(Bendixen et al., 2001; Cerrato et al., 2004). People with

sickle cell disease are also at high risk of ischemic

stroke, with 7–10% of people with this disease having

strokes before the age of 20 years (Adams, 1995). Those

with other hemoglobinopathies are at lesser risk of

stroke (Ohene-Frempong et al., 1998). Inherited throm-

bophilias, such as deficiencies in protein C, protein S,

antithrombin III, and factor V and II mutations, are risk

factors for venous thromboembolism but appear not to

be for stroke (Hankey et al., 2001).

17.3.2.5. Migraine

Migraine is a risk factor for ischemic stroke in young

adults aged less than 45 years with a relative risk of

2.36 (95%CI 1.92–2.90) (Etminan et al., 2005). The risk

of ischemic stroke associated with migraine is poten-

tiated among women, tripled among women who

smoke, and quadrupled among those taking the oral con-

traceptive pill. The triad of migraine, smoking, and oral

contraceptive pill use may increase the risk of ischemic

stroke 30-fold (Bousser, 2004; Etminan et al., 2005).

17.3.2.6. Drugs

Sympathomimetic agents in over-the-counter cold

remedies and herbal medications have been associated

with hemorrhagic stroke (Kernan et al., 2000). Illicit

drugs are a rare cause of stroke in older adults but may

cause up to 5% of stroke in people aged 15–44 years

(Sloan et al., 1998). Cocaine, amphetamines, heroin,

344 J.W. STU

and phencyclidine have been implicated. Potential

mechanisms of stroke include acute hypertension, vaso-

constriction, cerebral vasculitis, and cardiomyopathy.

Sympathomimetic drugs may also promote rupture of

aneurysms or arteriovenous malformations (Bendixen

et al., 2001).

17.3.3. Prognosis

17.3.3.1. Mortality

In most studies case fatality at 30 days post-stroke in

young adults (aged <45 years) is 10–23% (Jacobs

et al., 2002), similar to that in the general stroke popu-

lation (Thrift et al., 2000; Jacobs et al., 2002). Greater

30-day case fatality has been reported in South African

blacks (34%; Rosman, 1986), US blacks (33%; Jacobs

et al., 2002), and in hemorrhagic subtypes (intracerebral

hemorrhage 36%, subarachnoid hemorrhage 12%,

ischemic stroke 6%; Thrift et al., 2000; Jacobs et al.,

2002). Young stroke survivors remain at greatly

increased risk of death over the subsequent 10 years

compared to those of the same age and sex in the general

population, although estimates are imprecise because of

the small number of deaths occurring (OR 77.8; 95% CI

20.2–135.4; Hardie et al., 2003). Among those aged 15–

45 years with ischemic stroke, average annual mortality

rates are approximately 5% in the first year and 1% per

year thereafter (Marini et al., 1999; Leys et al., 2002;

Varona et al., 2004).

17.3.3.2. Stroke recurrence, myocardial infarction,

and seizures

The average annual rate of stroke recurrence for young

adults with ischemic stroke (1.4–3.6% in the first year

and 0.5–1.7% thereafter; Marini et al., 1999; Leys

et al., 2002; Varona et al., 2004) is lower than among

older people with stroke (12.5% at 1 year, average

of 3% per year thereafter; Hankey et al., 1998). Aver-

age annual rates of myocardial infarction are between

0.2% (Leys et al., 2002) and 1.7% (Marini et al.,

1999). An annual rate of vascular death, recurrent

stroke, or non-fatal myocardial infarction was reported

to be 2.6% over 6 years (Kappelle et al., 1994).

Post-stroke seizures occur in 6.6–10% of survivors

(Leys et al., 2002; Naess et al., 2002; Varona et al.,

2004).

17.3.3.3. Functional outcome

Of surviving young adults, more than 90% return to

independent living after stroke (Leys et al., 2002; Var-

ona et al., 2004), a much greater proportion than in the

general stroke population. However, only 42–58% were

employed at 6–12 years post-stroke (Kappelle et al.,

ET AL.

OU

1994; Naess et al., 2002; Varona et al., 2004),

one-quarter to one-half have depressive symptoms

(Kappelle et al., 1994; Varona et al., 2004), and the

majority report reduced quality of life (Kappelle et al.,

1994).

17.3.4. Summary

In summary, people aged less than 45 years with

stroke require special consideration. The frequencies

of underlying etiology differ from the older stroke

population and a greater breadth of investigation is

generally required (e.g., transesophageal echocardio-

graphy, angiography, antiphospholipid antibodies).

Young adults with stroke have fewer comorbidities

than older patients and have a better prognosis for

long-term survival and return to independence. None-

theless, the burden of stroke on young adults, their

families, and society is considerable, with approxi-

mately half never returning to employment and the

majority living with reduced quality of life.

17.4. Childhood stroke

Although considered a rare disorder by adult stan-

dards, childhood stroke (stroke in those aged <15years) is more common than brain tumors and is

among the top 10 causes of death in childhood, with

the highest mortality in the first 12 months of life

(Murphy, 2000). In comparison to adult stroke there

is limited understanding of the etiology, treatment,

and predictors of outcome of childhood stroke. Sys-

tematic coordinated care and research are only now

being initiated for these children.

17.4.1. Incidence

17.4.1.1. Arterial ischemic stroke

The incidence of stroke has increased over time, partly

because of better diagnosis due to increased awareness

and improved neuroimaging techniques (Lynch et al.,

2002). The best epidemiological data on childhood

stroke comes from the Canadian Pediatric Ischemic

Stroke Registry (CPISR; deVeber, 2000), showing an

incidence of arterial ischemic stroke of 2.7/100 000

population per year with a male to female ratio of

1.5:1. The stroke recurrence rate is as high as 20–40%

and recurrence is more likely with vasculopathies such

as sickle cell and Moyamoya disease. The age distribu-

tion of children with arterial ischemic stroke is skewed,

with approximately 25% occurring in infants less than 1

year of age (deVeber, 2000). Neonatal arterial ischemic

stroke (in infants<28 days of age) has an estimated inci-

dence of 1:4000 live births per year (Estan and Hope,


1997) but a lower recurrence rate, estimated at 3–5%.

It is under-recognized, with seizures the most common

mode of presentation. Hemiparesis is rarely noted,

occurring in less than 25% of newborns with stroke

(deVeber, 2000).

17.4.1.2. Sinovenous thrombosis

In the CPISR sinovenous thrombosis was less common

than arterial ischemic stroke, with an incidence of

0.67/100 000 per year. The age distributionwas skewed,

with infants less than 1 year of age comprising 54% of

cases and neonates 43% of cases. Thrombosis more

often involved the superficial venous system and was

associated with venous infarction in 41% of cases. In

76% of cases signs and symptoms were non-specific,

including headache, altered consciousness, and papille-

dema. Seizures were reported in 58% of children (deVe-

ber et al., 2001). Neonatal sinovenous thrombosis has an

estimated incidence of 41/100 000 population per year

(deVeber, 1999) with seizures and lethargy the most fre-

quent presentation. Clot propagation can occur without

clinical signs of deterioration. Infarction has been

reported in 50% and intraventricular hemorrhage in

33% of cases (Wu et al., 2003).

17.4.1.3. Hemorrhagic stroke

Hemorrhagic stroke has an estimated incidence of 1.5–

2.9/100 000 population per year (Broderick et al.,

1993; Lynch et al., 2002). In a series of 63 children

the most common presenting symptoms were head-

ache or vomiting due to raised intracranial pressure

(59% of cases), followed by seizures (37%) and hemi-

paresis (16%) (Al-Jarallah et al., 2000). Arteriovenous

malformations and fistulae are the most commonly

identified cause of hemorrhagic stroke and are asso-

ciated with a 2–4% risk of re-bleeding per year (Fults

and Kelly, 1984). Other causes of hemorrhagic stroke

include hematological disorders, coagulopathies,

trauma, brain tumors, cavernomas, and, rarely, aneur-

ysms (Lynch et al., 2002).

17.4.2. Risk factors for arterial ischemic strokeand sinovenous thrombosis

Risk factors for childhood arterial ischemic stroke are

age-dependent and include arteriopathies, cardiac disor-

ders, congenital or acquired thrombophilia, local or sys-

temic infections, and rare genetic/metabolic disorders

(Table 17.3). The majority of childhood stroke occurs

in those with pre-existing medical conditions (Chabrier

et al., 2000; Kirkham et al., 2000), the type and fre-

quency of which differ between countries. In 22–26%

of children with arterial ischemic stroke no identifiable


Table 17.3

Risk factors for childhood arterial ischemic stroke

Arteriopathies

(30–53)*

Acute transient vasculopathies—

post-varicella angiopathy

Moyamoya—primary or secondary

(neurofibromatosis, Down’s

syndrome)

Sickle cell disease

Arterial dissection

Primary angiitis of the central

nervous system

Fibromuscular dysplasia

Systemic vasculitides—SLE,

polyarteritis nodosa, Wegener’s

granulomatosis

Post-irradiation

Cardioembolic

stroke (4–24){Congenital heart disease

Acquired heart disease—

cardiomyopathy, rheumatic heart

disease, endocarditis

Thrombophilias

(18–38){Protein C deficiency

Protein S deficiency

Antithrombin III deficiency

Factor V Leiden mutation

Prothrombin 20210A mutation

Antiphospholipid syndrome

Inborn errors of

metabolism

Mitochondrial cytopathies—MELAS

Homocystinuria

Fabry disease

Congenital disorders of

glycosylation

Other Migrainous infarction

Bacterial meningitis

Hypertension

No etiology identified (22–26)}

MELAS, myopathy, encephalopathy, lactic acidosis, and stroke-like

episodes; SLE, systemic lupus erythematosus.

The study-specific figures obtained are:

*30% (deVeber, 2000) and 53% (Chabrier et al., 2000);{4% (Ganesan et al., 2003), 12% (Chabrier et al., 2000), and 24%

(deVeber, 2000);{18% (deVeber, 2000) and 38% (deVeber et al., 1998);}22% (Chabrier et al., 2000), 25% (Williams et al., 1997), and 26%

(deVeber, 2000).

346 J.W. STURM

cause can be found (Williams et al., 1997; Chabrier

et al., 2000).

In the CPISR 24% of cases were due to cardiac

causes, 30% to arteriopathies, 12% to systemic illness,

and 18% to hematological causes. No etiologywas iden-

tified in 26% of cases (deVeber, 2000). The presence of

multiple risk factors predicts poor outcome (Lanthier

et al., 2000).

The mechanism of neonatal arterial ischemic stroke

is also poorly understood. Risk factors include maternal

obstetric complications, perinatal events, sepsis, and

cardiac disorders (Lynch et al., 2002), and thrombo-

philic disorders have been reported in 25–68% of cases

(Monagle et al., 2004).

Risk factors for childhood sinovenous thrombosis

include dehydration, local head and neck or systemic

infections, congenital heart disease, and anemia. In a

study of 160 children prothrombotic abnormalities

were identified in 32% of cases (deVeber et al.,

2001); however, in another study prothrombotic

abnormalities were not found more frequently in cases

than in healthy controls (Kenet et al., 2004). Risk fac-

tors for neonatal sinovenous thrombosis include

asphyxia, chorioamnionitis, congenital heart disease,

polycythemia, sepsis, and dehydration (Wu et al.,

2003). Thrombophilia defects have been reported in

20% of neonates (deVeber et al., 2001).

17.4.2.1. Cardioembolic disease

Cardioembolic causes account for between 4% and

24% of childhood stroke (Chabrier et al., 2000; deVe-

ber, 2000; Strater et al., 2002; Ganesan et al., 2003).

This occurs more commonly in children with cyanotic

or complex congenital heart defects, particularly with

right to left shunt or polycythemia. Strokes can occur

spontaneously or during cardiac procedures. However,

unsuspected cardiac abnormalities are uncommonly

identified on echocardiogram in previously healthy

children (Ganesan et al., 2003) and there are insuffi-

cient data to determine whether minor cardiac defects

such as atrial septal defects or patent foramen ovale

are risk factors for arterial ischemic stroke (Kirkham

et al., 2000). Genetic conditions such as Marfan’s syn-

drome, tuberous sclerosis, Ehlers–Danlos syndrome,

muscular dystrophies, hereditary cardiomyopathies,

and conduction defects can also be associated with

cardioembolic stroke (Pavlakis et al., 2000).

17.4.2.2. Vasculopathies

Vasculopathies are a major cause of arterial ischemic

stroke, occurring in up to 53% of children with stroke

(Chabrier et al., 2000) and accounting for up to 80% of

cases once cardiac causes are excluded (Sebire et al.,

2004). They can be classified into acute non-progressive

disorders such as post-varicella angiopathy and arterial

dissection, and chronic vasculopathies such as moya-

moya and sickle cell disease.

Acute, transient cerebral arteriopathies are the

most common type of angiopathy. In a series of

59 children, cerebral arteriopathies were identified

on magnetic resonance angiography or conventional

angiography in more than a quarter of cases. All chil-

dren presented with hemiplegia and had subcortical

ET AL.

OU

stroke identified on neuroimaging (Chabrier et al.,

1998). Post-varicella angiopathy is the best described

form of this condition. A greater proportion of chil-

dren with a history of varicella in the previous 12

months had stroke when compared to control in a

French study (Sebire et al., 1999) and a causal rela-

tionship was subsequently confirmed in a prospective

Canadian cohort study (Askalan et al., 2001). Post-

varicella angiopathy typically causes focal or segmen-

tal stenosis of the distal internal carotid or proximal

segment of the middle cerebral artery resulting in

basal ganglia infarction (Askalan et al., 2001). Chil-

dren can have recurrent strokes up to 8 months fol-

lowing presentation but the arteriopathy takes a

monophasic course with subsequent regression of ste-

nosis within 2 years (Sebire et al., 1999; Lanthier

et al., 2005).

Moyamoya accounts for 7–20% of infarcts in chil-

dren and is most commonly seen in the Japanese popu-

lation (Chabrier et al., 2000). Angiography shows

progressive bilateral distal internal carotid artery ste-

nosis and occlusion with the development of a network

of collateral vessels forming the characteristic ‘puff of

smoke’ (Fig. 17.2). In children, Moyamoya is usually

associated with progressive motor and cognitive dete-

rioration, seizures, transient ischemic attacks, and

arterial ischemic stroke, in contrast to adults, where

hemorrhagic stroke is more common (Suzuki and

Kodama, 1983). Neurofibromatosis type 1, Down’s

syndrome, and tuberous sclerosis have also been asso-

ciated with Moyamoya disease.

Sickle cell disease is associated with distal internal

carotid or proximal middle cerebral artery stenosis.

Patients with sickle cell disease have a 10% untreated

risk per year of stroke (Adams et al., 1998) and at least

10% of homozygotes will have a stroke by 20 years of

age (Ohene-Frempong et al., 1998). Recurrent transi-

ent ischemic attacks and transcranial Doppler veloci-

ties above 200 cm/s are predictive of stroke (Adams

et al., 1997). These strokes can be prevented by regu-

lar transfusion to reduce sickle hemoglobin below

30% (Adams et al., 1998).

Arterial dissection accounts for 9–20% of cases of

arterial ischemic stroke. It more often involves the

intracranial and anterior circulations (Fullerton et al.,

2001).

Primary angiitis of the central nervous system has

been rarely described in children. This progressive

disorder has a high mortality rate. Children with

large- to medium-sized artery involvement and evi-

dence of granulomatous angiitis on biopsy have a

poorer outcome than those with small-vessel involve-

ment and a lymphocytic inflammatory infiltrate (Lan-

thier et al., 2001). Other rare causes of vasculopathy


include postcranial irradiation arteriopathy and fibro-

muscular dysplasia.

17.4.2.3. Thrombophilias

The thrombophilias are congenital or acquired states that

increase the risk of thromboembolic disease. The most

common congenital thrombophilic defect in the general

population is caused by a mutation in clotting factor V

that makes it resistant to the inhibition of activated pro-

tein C (activated protein C resistance, factor V Leiden

mutation; Bertina et al., 1994). A mutation in the precur-

sor of thrombin (prothrombin gene mutation) is another

well established congenital thrombophilic defect (Poort

et al., 1996). The most common acquired thrombophilic

defect is development of antiphospholipid antibodies

(Ehrenforth et al., 1999; Greaves, 1999). They occur tran-

siently following tissue injury, infection, and drug expo-

sure or develop as part of a broader autoimmune

disease. Antiphospholipid antibodies are associated with

an increased risk of arterial and venous thromboembo-

lism as well as an increased risk of stroke in adults.

Recently, an increase in the frequency of thrombo-

philia in children with stroke has been reported (Angel-

ini et al., 1994; Ganesan et al., 1996; Becker et al., 1998;

Bonduel et al., 1999; Heller et al., 1999; Nowak-Gottl

et al., 1999a, b; Strater et al., 1999). Prothrombotic

abnormalities have been identified in 38% of children

with acute stroke (deVeber et al., 1998) and may indi-

cate increased risk of recurrence (Chabrier et al.,

1998). Others, however, have found no relationship

between prothrombotic abnormalities and stroke (Gane-

san et al., 1998; Zenz et al., 1998; McColl et al., 1999).

Many of these studies hadmethodological flaws, includ-

ing highly selected, non-prospective populations and a

lack of systematic thrombophilic work up on all

patients. Acquired protein S deficiency is known to

occur after varicella infection and may explain the

increased incidence of childhood stroke following

chicken pox infection (Humphries, 1995). Elevated

anticardiolipin antibodies do not seem to be associated

with childhood stroke (Lanthier et al., 2004). Impor-

tantly, no investigators have documented a relationship

between thrombophilia and severity, recurrence, or

neurological outcome of arterial ischemic stroke.

17.4.2.4. Other causes

Raremetabolic causes of arterial ischemic stroke include:

homocystinuria; mitochondrial disorders such as mito-

chondrial myopathy, encephalopathy, lactic acidosis,

and stroke-like episodes (MELAS); Fabry’s disease, an

X linked lysosomal disorder; congenital disorders of gly-

cosylation; urea cycle defects; and amino and organic

acidemias (Pavlakis et al., 2000).


RM

17.4.3. Outcome following stroke

The outcome of childhood arterial ischemic stroke is

worse than for sinovenous thrombosis. The reported

mortality for arterial ischemic stroke ranges from 7%

to 28% (Lynch et al., 2002), with death being caused

either by the stroke or by the underlying disease. The

reported frequency of long-term neurological deficits

following childhood arterial ischemic stroke ranges

from 50% to 85%, with post-stroke epilepsy occurring

in 15–20% of survivors. Stroke recurs in approximately

19–40% of children with arterial ischemic stroke (deVe-

ber, 2000; Ganesan et al., 2000). Factors associated with

greater risk of recurrent stroke include recurrent tran-

sient ischemic attacks, Moyamoya disease, vasculitis,

5–10 methylenetetrahydrofolate reductase homozygos-

ity, elevated homocysteine, anticardiolipin antibodies,

systemic disease, and embolic stroke (Chabrier et al.,

2000; Lynch et al., 2002). In children with middle cere-

bral artery strokes there is correlation between an infarct

volume of more than 10% (Ganesan et al., 1999),

younger age at time of stroke (Ganesan et al., 2000),

and poor outcome.

A 10% mortality has been reported in neonatal arter-

ial ischemic stroke, and two-thirds have neurological

deficits (deVeber et al., 1995). Motor sequelae includ-

ing hemiplegia, dystonia, and spasticity occur less fre-

quently in neonates than in older children but are more

likely if there is concomitant involvement of the basal

ganglia, internal capsule, and cortex (Mercuri et al.,

1999). Recurrence risk is lower than in older children,

occurring in fewer than 5%.

The outcome of childhood sinovenous thrombosis,

although better than for arterial ischemic stroke, is

still guarded. In the CPISR there was 8% mortality,

with death being directly attributable to sinovenous

thrombosis in one-quarter of children. Some 38%

had neurological deficits, including motor impair-

ment, cranial nerve palsies, or delayed intellectual

development, and 15% had seizures. The presence

of venous infarct predicted a worse outcome (deVe-

ber et al., 2001). In a multicenter European study of

42 children there was 12% mortality and 62% had

neurological sequelae. Older age, absence of venous

infarction, anticoagulant therapy, and lateral and/or

venous sinus involvement were independent predic-

tors of good outcome (Sebire et al., 2005). By con-

trast 74% of neonates have no neurological sequelae

(deVeber et al., 2000).

There is scarce literature on the functional impact

of childhood stroke. In a study of 17 children with

unilateral middle cerebral artery territory stroke, 47%

had mild to moderate activity limitations affecting

motor function, self-care, and education. There were

348 J.W. STU

correlations between impairment of bodily functions

and activity limitation, and between the extent of brain

injury on neuroimaging and physical health (Gordon

et al., 2002).

Cognitive outcome following stroke has been exam-

ined in a few studies. In a Canadian series of 163 neo-

nates and children with arterial ischemic stroke and

sinovenous thrombosis, speech and cognitive deficits

were rare (deVeber et al., 2000); however, in a UK series

of 90 children, 59% had educational difficulties and

42% had speech and language deficits (Ganesan et al.,

2000). Higher cortical function impairments are also

common in children with congenital hemiplegia due to

presumed perinatal strokes, with 54% having speech,

behavior, or learning problems and 23% having seizures

(Golomb et al., 2001).

First-year costs of stroke for adult patients have been

estimated to be US$14 361 (Dewey et al., 2001). The

types and magnitude of health care costs generated by

childhood stroke have not been assessed but are likely

to be much greater than in adults because children sur-

viving stroke will have more years living with disabil-

ity. The psychological and social impact of childhood

stroke has not been estimated and warrants further

study.

ET AL.

17.4.4. Summary

Although considered rare, stroke is more common

than brain tumors in children. One-quarter of arterial

ischemic stroke and more than half of sinovenous

thrombosis cases occur in children less than 1 year of

age. Arteriopathies are the most commonly identified

risk factor for arterial ischemic stroke, followed by car-

diac and thromboembolic disorders. Neurological

sequelae are common in arterial ischemic stroke and

sinovenous thrombosis.

Prospective registries are necessary to increase

understanding of childhood stroke and to establish accu-

rate recurrence risks. Outcome studies using validated

measures are needed to determine the long-term impact

of stroke on children and their families, and to plan

interventional studies to improve the outcome of chil-

dren with stroke. Because of the relatively small number

of strokes that occur in children, multicenter collabora-

tion will be required to ensure that adequate cases are

accrued. Such a collaboration, termed the International

Pediatric Stroke Study, has been formed through a

consortium of pediatric neurologists and hematologists

who are currently enrolling patients in an international

childhood stroke registry. A multicenter randomized

controlled trial of aspirin versus Coumadin in the sec-

ondary prevention of childhood stroke is also planned

OUPS, YOUNG ADULTS, AND CHILDREN 349

to assess whether childhood stroke can be prevented

(International Pediatric Stroke Study: https://www.sick-

kids.on.ca/cstrokestudy).

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