Ischemic Stroke Young Adults

Epidemiology and Etiology of Ischemic Stroke in Young Adults Aged 18 to 44 Years in Northern Sweden
4/28/16, 7:16 PM
Stroke
stroke.ahajournals.org
Stroke. 1997; 28: 1702-1709
doi: 10.1161/01.STR.28.9.1702
Articles
Epidemiology and Etiology of Ischemic Stroke in Young Adults Aged
18 to 44 Years in Northern Sweden
Bo Kristensen
Kristensen,, MD
MD;; Jan Malm
Malm,, PhD
PhD;; Bo Carlberg
Carlberg,, PhD
PhD;; Birgitta Stegmayr
Stegmayr,,
PhD
PhD;; Christer Backman
Backman,, MD
MD;; Markku Fagerlund
Fagerlund,, PhD
PhD;; Tommy Olsson
Olsson,,
PhD
+ Author Affiliations
Correspondence to Bo Kristensen, MD, Department of Neurology, University

Hospital, S-901 85 Ume, Sweden. E-mail Bo.Kristensen@neuro.umu.se
Abstract
Background and Purpose The aim of this study was to conduct a population-based
epidemiological survey among young adults aged 18 to 44 years in Northern
Sweden and furthermore to gain further insight into the etiology of ischemic
stroke in this age group.
Methods Two studies were done. In the first part, epidemiological data were
collected to calculate incidence and mortality from 1991 through 1994. This was
based on the World Health Organization Northern Sweden MONICA register of
acute stroke events. Eighty-eight first-ever ischemic stroke patients were
identified during that period. In the second part, 107 consecutive patients aged
18 to 44 years with ischemic stroke referred to a university hospital were studied
prospectively during a 5-year period and were extensively evaluated according to
a standardized protocol. On the basis of modified Trial of ORG 10172 in Acute
Stroke Treatment (TOAST) criteria, the patients were classified into eight subtypes
of ischemic stroke.
Results The average population-based annual incidence rate for ischemic stroke
(cases per 100 000 per year) was 11.3 (95% confidence interval, 6.7 to 16.1). The
case-fatality rate was 5.7%. According to the modified TOAST criteria, a probable
cause of ischemic stroke was identified in 36% and remained unexplained in 21%
of cases. Spontaneous cervical arterial dissection was the leading probable
etiology (13%). Patent foramen ovale or atrial septal aneurysm was a possible
cause of stroke in 28% of cases. The percentages of ischemic stroke attributed to
IgG anticardiolipin antibodies (4.7%), atherothrombotic vasculopathy (3.7%), oral
contraceptive use (7%), and migraine (1%) were lower than reported in recent
clinical series.
Conclusions The incidence rate for ischemic stroke was higher than previously
reported from most countries in Western Europe. The higher incidence was not
explained by a higher prevalence of premature atherosclerotic vasculopathy.
Without the additional diagnostic information derived from advanced cardiac
imaging, the proportion of indeterminate cases would have constituted 37% of the
patients.
Key Words:
cerebral infarction
epidemiology
stroke classification
Sweden
young adults
Ischemic stroke in young adults has been considered a relatively rare event, with
1
http://stroke.ahajournals.org/content/28/9/1702.long
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fewer than 5% of all cerebral ischemic infarctions occurring below the age of 45
2
years, although more than 10% has been reported. The age-specific incidence of
stroke among individuals in this young age group has been reported by
community and hospital surveys from various geographic areas. However, hardly
3
any population-based data have been reported.
The causes of stroke among young adults are more diverse than in the elderly and
require a thorough diagnostic workup. A major problem has thus been that
previous studies addressing the etiology of ischemic cerebral infarction in the
young have often been retrospective and nonstandardized, with highly variable
4
investigational techniques and sets of diagnostic criteria being applied. In
addition, advances in technology, including transesophageal investigation and
new biochemical assays, have introduced new potential causes of ischemic stroke
that still need to be substantiated. Finally, without the acknowledgment of cases
not referred for investigation, a biased pattern of the causes of the disease may
be present in hospital-based studies from third-level facility hospitals.
The objectives of the present study were to evaluate a true age-specific incidence
and furthermore to delineate the causes of ischemic stroke in young adults. The
study was thus undertaken in two parts. First, a prospective population-based
epidemiological survey was conducted to provide data on the incidence and
mortality rates of ischemic stroke in young adults from northern Sweden. Second,
in a series of patients admitted to our university hospital, an accurate hierarchy of
causes of ischemic stroke was established on the basis of the TOAST classification
5
modified for ischemic stroke in young adults.
Subjects and Methods

Epidemiological Study
Acute stroke events in the two northernmost counties of our catchment area (Fig
1) have been monitored since 1985 by the WHO Northern Sweden MONICA
6
project. The case finding and validation of data quality have been described in
7
detail earlier.
Figure 1.
Map of Sweden displaying the
MONICA surveillance area for
Northern Sweden (dark gray
color) and the catchment area
of Ume University Hospital.
Eighty-eight patients were
included during 1991 to 1994
from the MONICA register for
the epidemiological part of the
study. One hundred seven
View larger version:
patients were recruited and
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evaluated from the catchment
area of Ume University
Hospital during 1991 to 1996
for the etiological part of the study. This includes the 71 patients from
the MONICA surveillance area evaluated between 1991 and 1994.
The total population in the MONICA surveillance area was 518 669 on January 1,
1991, and 527 423 on December 31, 1994. The target population considered to
be at risk included all residents aged 18 to 44 years in this area. They represented
37% (194 194 and 193 113, respectively) of the total population at the beginning
and at the end of the epidemiological survey period.
Clinical information from discharge records on all subjects in the age range 25 to
45 years with ICD-9 codes 430 to 438 was screened and validated for acute
stroke events that met the definition of ischemic stroke. Data from the group aged
18 to 25 years not originally computed in the MONICA register were obtained,
adhering to the same guidelines. This part of the study thus contains patients
referred to our university hospital (included in the etiological study; see below) as
well as patients investigated only at local acute-care hospitals in Northern
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Sweden. The same inclusion and exclusion criteria as in the etiological study were
used.
Etiological Study
Northern Sweden is served by 13 local hospitals and a third-level university
hospital (Fig 1). The population in the present study consists of patients aged 18
to 44 years who were admitted to Ume University Hospital between January 1991
and May 1996 as a result of ischemic stroke. The inclusion criteria were as
follows: (1) first-ever completed ischemic stroke, defined as a rapidly developing
focal neurological deficit with no apparent cause other than a vascular origin, that
persisted beyond 24 hours in surviving patients; (2) age from 18 through 44
years; and (3) evaluation possible within 3 months after stroke onset. Patients
were scheduled for follow-up at 4 and 12 months after admission. Exclusion
criteria were as follows: ischemic stroke due to complications of subarachnoid
hemorrhage, cardiac surgery, and malignancy in a terminal stage or occurring as
an immediate consequence of trauma.
Clinical and Laboratory Evaluation
Medical history and information regarding cerebrovascular risk factors such as
arterial hypertension, diabetes mellitus, smoking, alcohol use, illicit drug use,
hyperlipidemia, oral contraceptive use, history of migraine, and occurrence of
venous or arterial thrombosis in the family were obtained according to a
standardized protocol. Hypertension was defined as systolic blood pressure >160
mm Hg and/or diastolic pressure >95 mm Hg on two different occasions
measured outside of the acute phase of stroke or treatment with antihypertensive
drugs during the last 2 weeks before recruitment; diagnosis of diabetes mellitus
was documented by medical records or at recruitment according to the WHO
8
criteria ; hypercholesterolemia was considered present if fasting blood level was
6.5 mmol/L at recruitment; and hypertriglyceridemia was present if fasting
triglyceride levels were >2.2 mmol/L at recruitment. Current smoking was defined
as smoking one or more cigarettes per day. Migraine was defined according to the
9
criteria of the International Headache Society.
Neuroimaging included CT and MRI of the brain, assessment of cerebral blood
flow (single-photon emission CT with Tchexamethylpropyleneamine oxime), and
cerebral angiography including posterior circulation angiography. Furthermore,
duplex ultrasonography of the cervical arteries, chest roentgenography,
electrocardiography, and 24-hour Holter electrocardiography recording was
performed.
In reference to echocardiographic studies, the TTE studies were performed with
the use of standard techniques. Views were obtained in the parasternal, apical,
and subcostal windows. The TEE images were obtained with a 5-MHz monoplane
transducer in 69 patients and with a multiplane transducer in 28 patients. All
examinations were recorded on videotape and analyzed in a blinded manner offline in a random order. ASA was diagnosed when the atrial septum appeared
abnormally redundant and mobile and exhibited an excursion into the left or right
atrium, or both, of >10 mm and a base of 10 mm. For PFO, the
echocardiographic detection of interatrial right-to-left shunting was identified by
color-flow Doppler or by the administration of 5 mL agitated saline in an
antecubital vein. Two to four contrast injections were systematically performed in
each patient, in the resting state and during provocative maneuvers (Valsalva and
cough test) to transiently reverse the interatrial pressure gradient. The
echocardiographic diagnosis of PFO was based on the appearance of at least three
microcavitations, either spontaneously or after provocation maneuvers, into the
left atrium, not later than four cycles after the appearance of the microcavitations
in the right atrium. The presence of atheroma of any severity was noted when
detected on echocardiography, occurring between the aortic valve and the origin
of the left subclavian artery. Mitral valve prolapse was defined on TTE as mitral
leaflet thickening and displacement beyond the plane of the mitral annulus and
into the left atrium in the parasternal long-axis view during systole.
A detailed laboratory study was performed, including complete blood cell count;
electrolytes; serum creatinine; amino-transferases; creatine kinase; urinary
analysis; erythrocyte sedimentation rate; serum protein electrophoresis;
concentrations of blood glucose and glycosylated hemoglobin; antinuclear
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antibodies and IgG aCLs; rheumatoid factor; complement factors (C3/C4);

serological testing for syphilis, borreliosis, and viral infections, including HIV;
serum cholesterol and triglyceride levels; LDL and HDL levels; lipoprotein(a); and
prothrombin and activated partial thromboplastin times. Activated partial
thromboplastin time was also used as a screening test for the presence of lupus
anticoagulants. Levels of protein C, protein S, and antithrombin III were analyzed
both in the acute phase and at least 4 months after first admission.
Classification of Subtypes
We used a modified stroke subtype classification for the etiology of ischemic
stroke with the definitions based on the TOAST classification, accommodated and
5
validated for stroke in the young. The patients were classified independently by
two groups of paired investigators. A consensus approach was applied when
necessary. The main diagnostic criteria are presented in Fig 2.
Figure 2.
Causes of ischemic stroke in
young patients evaluated at
Ume University Hospital in the
etiologic (*, n=71) and the
epidemiological (**, n=107)
parts of the study. The lowerpriority diagnoses were not to
be coded as probable when a
higher-priority probable or
possible diagnosis was present,
View larger version:
but there could be two probable
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diagnoses if criteria for two
conditions of equal priority were
met. IHS indicates International
Headache Society; APLA, antiphospholipid antibodies.
Statistical Analyses
Incidence rate was derived from the number of first episodes of ischemic stroke
among the residents in the two counties during the study period. The average of
the populations living in the area between January 1, 1991, and December 31,
1994, was the denominator of the equations for the incidence rates. Case-fatality
rate was defined as the number of subjects who died within 28 days from the
onset of stroke during the same period. Ninety-five percent confidence intervals
were computed according to the Poisson variation for the number of events within
2
the age groups. Fishers exact and tests were used when appropriate for
statistical analysis. Probability was two tailed, and P<.05 was considered
significant.
The study was approved by the Research Ethics Committee of Ume University;
data handling procedures were approved by the National Computer Data
Inspection Board.
Results
Epidemiological Study
A total of 88 first-ever ischemic strokes in the age range 18 through 44 years
from the MONICA surveillance area were recognized during the time period of
January 1, 1991, to December 31, 1994. Seventy-one cases (81%) were primarily
evaluated or referred from secondary-level care settings for further investigations
at the university hospital. These patients are thus included in the etiologic study
part. The additional 17 cases, all admitted to local acute-care hospitals, were
identified from the MONICA project register. These additional cases had all
undergone CT scan or necropsy. No further cases were recognized from death
certificates only or from medical discharge records in the group aged 18 to 24
years.
The average annual incidence rate of first-ever ischemic stroke in the group aged
18 to 44 years was 11.3/100 000. The age- and sex-specific incidence rates and
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the 95% confidence intervals are shown in Table 1. In both sexes the risk of
stroke increased with age, but there was no statistically significant difference
2
between men and women ( =3.03, P=.08).
Table 1.
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Average Annual Age- and SexIn this window

Specific Incidence Rates of First
Ischemic Stroke in Young
Adults in Northern Sweden, 1991 to 1994
Five patients died within 28 days, resulting in a case-fatality rate of 5.7%. Deaths
resulted from ischemic cerebral edema and herniation in 3 patients and from the
effects of severe brain stem cerebellar infarction in 1 patient. One patient died as
a result of a myocardial infarction and subsequent congestive heart failure.
Data pertaining to the yearly average of ischemic stroke events in men and women
in the group aged 25 to 74 years during the time period 1991 to 1993 were
7
available from the MONICA register. On average, 562 first-ever ischemic stroke
events occurred yearly during 1991 to 1993. Ischemic stroke in young adults thus
represented 3.9% of all ischemic strokes in the group aged 18 to 74 years.
The distribution of the main diagnostic categories for the 71 patients evaluated at
the university hospital during the epidemiological survey period is shown in Fig
2. The mean age of the 17 patients (10 men, 7 women) not evaluated at our
university hospital was 40.22.3 years (range, 27 to 44 years). Based on
information from local hospital records on admission and on discharge, an
apparent probable diagnosis could be assigned to 3 patients. Because of
incomplete evaluation at the local- level hospitals, it was not possible to allocate
the remaining 14 patients to a particular etiologic subtype.
Etiology
In this part of the study, 63 men and 44 women referred to our hospital from
January 1, 1991, through May 31, 1996, fulfilled the inclusion criteria. The mean
age of the patients was 36.56.2 years (range, 19 to 44 years); age and sex
distribution is shown in Table 2. Unwillingness to participate in certain
procedures, technical problems, pregnancy, and early death explained why
scheduled investigations were not accomplished in all cases. Selective
angiography of both carotids and at least one vertebral artery was performed in
95 patients (89%), and abnormalities related to clinical symptoms were found in
58 patients (61%). In addition, 3 patients underwent MRI angiography. All patients
were investigated by CT, and 80 patients (75%) were investigated by MRI of the
brain. The carotid territory was involved in 56%, the posterior circulation was
affected in 41%, and multiple territories were involved in 3%. Six patients did not
display any visible ischemic lesions on neuroimaging. One hundred five patients
(98%) underwent either a TTE or TEE investigation.
Table 2.
Distribution by Age and Sex
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After completion of the etiologic workup, assessment of a probable or possible

etiology led to classification of the patients into one or more of eight diagnostic
groups subdivided into higher-priority (I to IV) and lower-priority (V to VIII)
diagnoses (Fig 2). The distribution of diagnoses relating to the specific age
groups of 18 to 34 years and 35 to 44 years is shown in Table 3. The main
finding was an increased occurrence of nonatherosclerotic vasculopathy in the
older age group.
Table 3.
Distribution of Probable and
Possible Causes of Ischemic
Stroke Among 107 Young
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Adults Divided into Two Subpopulations by Age at Time of Ictus
Risk factors were distributed as reported in Table 4. There were no statistically

significant differences between sexes with regard to atherosclerotic risk factors,
whereas migraine history was more frequently associated with female sex
(P=.041).
Table 4.
Distribution of Risk Factors
According to Sex
View this table:

Higher-Priority Diagnoses
Ninety higher-priority diagnoses were identified in 76 patients. In 14 patients two
higher-priority diagnoses coexisted. Atherosclerotic vasculopathy was diagnosed
as the cause of cerebral infarction in 13 patients (11%). Atherogenic risk factors
were present in all of these patients except 1. All patients with a possible
diagnosis of atherothrombotic vasculopathy demonstrated only discrete plaque
formation in the carotid arteries without any signs of flow abnormalities. In
addition, TEE revealed a simple aortic arch atheroma in 3 patients.
The main cause for nonatherosclerotic vasculopathy was nontraumatic
cervicocerebral arterial dissection. The carotid arteries were affected in 9 patients
and the vertebral arteries in 10 patients. One patient with fibromuscular dysplasia
as an underlying cause had bilateral carotid dissections. Isolated intracranial
arteritis was diagnosed in 1 patient. Coexistent higher-priority diagnosis was
found in 7 patients with probable or possible arterial dissection, 5 with a
PFO/ASA, 1 with low positive IgG aCL titer, and 1 patient with a simple aortic arch
atheroma, in which case priority in the final classification was given to the
diagnosis of arterial dissection.
A cardioembolic etiology was presumed in 35 patients (33%). The most frequent
abnormality was right to left cardiac shunts consistent with PFO, which became
evident in 32 of 97 patients (33%) investigated with TEE. In one patient PFO was
associated with pulmonary arteriovenous fistulas. Atrial septum aneurysm was
detected in 9 patients (9%), isolated in 5 patients, and associated with PFO in 4
patients. Angiographic lesions compatible with intracranial embolic occlusion were
detected in 16 of 30 patients (53%) with PFO/ASA as the possible cause of stroke.
Coexistent higher-priority diagnoses was found in 6 patients with PFO/ASA, 1
with a low positive IgG aCL titer and 5 with a possible atherothrombotic
vasculopathy, including 1 patient with a simple aortic arch atheroma, but in the
final classification priority was given to the cardioembolic diagnosis. Additionally,
6 patients with PFO/ASA had coexisting lower-priority diagnoses (lacunar
infarction [n=2], migraine-induced infarction [n=2], and oral contraceptive use
[n=2]). Mitral valve prolapse was observed in 1 patient. In 4 patients a probable
source of cardiac embolism was present (congenital heart disease [n=2], ischemic
dilated cardiomyopthy with left ventricular thrombus and PFO [n=1], and atrial
septum defect with left atrial thrombus [n=1]). There was no evidence of potential
emboligenic arrhythmias from electrocardiography or Holter monitoring.
With respect to hematological causes of stroke, natural anticoagulant levels were
determined for 102 patients at admission and for 97 patients at follow-up. One
patient had an inherited protein S deficiency. Seven patients (7%) had low positive
readings for IgG aCL. Other laboratory features such as ANA titers, VDRL tests,
complement C4, thrombocytes, and aPPT were negative or within normal range in
all IgG aCLpositive patients, and no valve abnormalities were detected by
echocardiographic investigation. A history of heavy alcohol ingestion within the
preceding 24 hours was elicited in 1 patient. Ischemic stroke occurred in the
postpartum state in 1 patient.
Lower-Priority Diagnoses
Thirteen patients met the criteria for lacunar infarct, ie, a lacunar syndrome and
small deep infarction compatible with small-artery disease. In 8 patients a
coexistent higher-order diagnosis was present (possible cardiac embolism [n=2],
possible atherothrombotic vasculopathy [n=5], and IgG aCL low-positive reading
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[n=1]).
Eighteen percent of men and 35% of women had a history of migraine, but only 1
woman fulfilled the criteria of the International Headache Society for a probable
9
migraine-induced stroke. Migraine-induced stroke was possible in an additional
3 patients with higher-priority diagnosis (possible cardiac embolism [n=2] and
probable arterial dissection [n=1]).
Oral contraceptive use was the likely cause of stroke in 3 female patients with
additional risk factors (smoking and migraine [n=1], smoking [n=1], and
hypertension [n=1]). Five women qualified for another diagnosis (possible cardiac
embolism
[n=2],
probable
arterial
dissection
[n=2],
and
possible
atherothrombotic vasculopathy [n=1]).
The etiology of cerebral infarction was indeterminate in 22 patients (21%). The
evaluation was truly negative except for 1 patient who did not have an
angiography and 1 patient who was unable to endure TEE but had a normal TTE
investigation. In this subgroup of patients, angiographic investigations were
abnormal in 12 patients (52%) with unexplained intracranial occlusion of a major
artery or a branch cortical artery. Overall, there was a preponderance of ischemic
lesions in the vertebrobasilar system (57%). Fourteen patients (61%) with an
indeterminate diagnosis had at least one risk factor for atherosclerosis (6 with one
and 8 with two or more atherogenic risk factors).
Discussion
The present study is one of the largest reported series of young adults with
ischemic stroke investigated by a group of physicians at a single medical center
and the first study of stroke in young individuals in which a clear populationbased strategy for case finding has been combined with a very extensive
diagnostic workup.
By international standards, the crude incidence rates for ischemic stroke in the
present study are higher than those reported earlier from most countries in
3 10 11 12
Western Europe
(Table 5) and similar to those among whites in
13
Baltimore, Md. One study from Israel has provided information from this decade
with an estimated incidence for ischemic stroke of 5/100 000 in the group aged
14
17 to 44 years. Our rates are only lower than the unusually high rates of stroke
15
among males and females aged 15 to 40 years of age in Benghazi, Libya, and
13
among blacks in Baltimore, Md.
The reported 50% higher incidence rates for
ischemic stroke in the elderly population of the Northern Sweden MONICA study
10
compared with available data from the MONICA study of Gothenburg, Sweden,
11
together with older limited data from the Stockholm region may suggest a south
to north stroke gradient in Sweden. The explanation for such a possible
geographic variation is currently unclear.
Table 5.
Age-Specific Incidence Rates
(per 100 000) of Ischemic
Stroke in the Young
View this table:

Similar to reports from other countries, incidence rates for both men and women
16
were found to rise steeply after the age of 35 years. In our study this increase
was mainly explained by an increase in the number of arterial dissections and
cardioembolic cases, but it was influenced to only a minor degree by an increase
in premature atherosclerosis (Table 3).
A case-fatality rate of 5.7% in the present study is considerably lower, as
expected, in comparison with elderly stroke patients but corresponds to case3 10
fatality rates reported for similar age groups in epidemiological studies
and
17 18
case series.
The topography of cerebral infarctions in young adults with ischemic stroke has
rarely been detailed in previous studies. The proportion of patients with
2 19
involvement of the vertebrobasilar territory has varied from 25% to 34%.
The
relatively high proportion of involvement of the vertebrobasilar territory in our
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study (41%) may at least partially be due to the extensive use of MRI
investigations. Thus, quite a few cases with ischemic lesions in this territory,
including cerebellar strokes, may have gone undetected in studies mainly relying
on CT scanning.
The criteria for atherosclerotic disease have varied considerably in previous
studies, and several studies included cases defined only by the coexistence of risk
factors for atherosclerosis, which may explain why atherosclerosis has been
considered to be the cause of stroke in 5% to 50% of patients younger than 50
17 20
years.
Using the TOAST classification, we detected 3.7% of patients with a
probable atherosclerotic vasculopathy; when similar criteria for probable
atherosclerotic vasculopathy were used, the rate of atherosclerotic etiology in
17 18 21 22 23
recent studies has varied from 5% to 23%.
Several recent studies have demonstrated that the presence of plaques 4 mm in
the aortic arch is an important new source of emboli to the brain in patients older
24
than 60 years.
However, this does not seem to be the case in a young stroke
population. This is consistent with the results reported from a few previous
25 26
studies including young as well as old stroke patients.
The use of duplex ultrasonographic and arteriographic evaluation of precerebral
and intracerebral vessels resulted in a diagnosis of cervicocerebral arterial
dissection in approximately 20% of patients, a proportion considerably higher
17 20 27
than reported in most earlier studies.
Our routine use of posterior
circulation angiography revealed that vertebrobasilar dissection was a common
cause of stroke in this age group. This emphasizes that a diagnosis of arterial
dissection should be considered in all cases of stroke in young adults and that a
thorough angiographic evaluation, including the vertebrobasilar territory, is
warranted in most cases.
28 29
The prevalence of PFO and ASA is increased in younger adults with stroke,
21 30
particularly in patients with otherwise unexplained stroke.
In those younger
than 45 years, a prevalence of PFO within the same range as in our study (24% to
26 30 31
50%) has been reported from three previous studies.
The mechanism
underlying thromboembolic events in patients with interatrial septum
21 32
abnormalities is not well known.
Angiographic evidence of embolic
intracranial arterial occlusions was present in 53% of our patients and gave some
evidence of a nidus for thrombus formation. It is of interest to note that 50% of
our patients with vertebral dissection had a PFO, an ASA, or both. It is thus
important to emphasize that significant vascular pathology must be excluded
before these cardiac abnormalities are accepted as the cause of stroke in each
individual case.
In our stroke population, hereditary deficiency of natural anticoagulants (protein
S, protein C, and antithrombin III deficiency) was very rarely encountered, which is
33
in agreement with results reported by Adams et al
but at variance with the
34 35
findings reported from small or selected case series.
Furthermore, the low
frequency and low titers of IgG aCL in the present study imply that these
antibodies do not account for a significant proportion of strokes in young people,
at least not in all young stroke populations. These findings are in agreement with
two recent larger prospective studies in which the relevance of aCL for ischemic
36 37
stroke in unselected stroke populations has been questioned.
However, in
respect to other hematologic causes of stroke, it is possible that factor V Leiden
gene point mutation could be of interest, although whether activated protein C
resistance secondary to this mutation causes arterial vascular disorder is still
38 39
controversial.
The definition of migraine-induced stroke applied in studies conducted thus far
has been inconsistent and probably explains why cerebral infarctions in the young
18 40 41
attributed to migrainous infarction have varied between 1.2% and 25%.
In
the present study only 1% of the patients (one patient), based on the criteria of the
9
International Headache Society, fulfilled the criteria for migrainous infarction,
although the prevalence of migraine with or without aura was higher than might
42 43
be expected from the background.
Based on data from our epidemiological
survey, the incidence of migraine-induced infarction meeting the criteria of the
International Headache Society can be estimated at 0.14/100 000 per year and
including possible migraine-induced infarction can be estimated at 0.7/100 000
per year in the group aged 18 to 44 years.
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The risk increment for cardiovascular disease, including stroke, among users of
44 45 46
oral contraceptives is currently a matter of controversy.
By ruling out
coexistent and more convincing etiologies such as cardioembolism and arterial
dissection, we could attribute a probable pathogenetic role to oral contraceptive
use in 7% of women.
Conclusions
We report a high incidence of stroke among young adults in Northern Sweden.
This finding is not explained by conventional causes of stroke, particularly not by
a high prevalence of premature atherosclerotic disease. Without the additional
diagnostic information derived from TEE contrast investigation, the proportion of
indeterminate cases would have constituted 37% of the patients. Nontraumatic
arterial dissection was a leading cause of ischemic stroke in our study. New
exciting data pointing toward the possibility that spontaneous cervical artery
dissections may be due to an underlying connective tissue disorder warrant
47
further investigations of this specific subgroup of patients.
Selected Abbreviations and Acronyms
aCL
ASA
ICD-9
=anticardiolipin antibodies
=atrial septal aneurysm
=International Classification of
Diseases, 9th Revision
MONICA=Monitoring Trends and
Determinants in Cardiovascular
Disease
PFO
=patent foramen ovale
TEE
=transesophageal
echocardiography
TOAST =Trial of ORG 10172 in Acute
Stroke Treatment
TTE
=transthoracic echocardiography
WHO
=World Health Organization
Acknowledgments
This study was supported by the Swedish Medical Research Council (grant K9719X-12237-01A to Dr Olsson), Karl-Oskar Hanssons Foundation, the Swedish
Society of Neurologically Disabled (NHR), 1987 Stroke Foundation,
Norrlandsfonden, and the Swedish Heart and Lung Foundation.
Received January 27, 1997.
Revision received May 15, 1997.
Accepted May 16, 1997.
Copyright 1997 by American Heart Association
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Ischemic Stroke Young Adults

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Epidemiology and Etiology of Ischemic Stroke in Young Adults Aged 18 to 44 Years in Northern Sweden

Correspondence to Bo Kristensen, MD, Department of Neurology, University

Subjects and Methods

antibodies and IgG aCLs; rheumatoid factor; complement factors (C3/C4);

Average Annual Age- and SexIn this window

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After completion of the etiologic workup, assessment of a probable or possible

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Adults Divided into Two Subpopulations by Age at Time of Ictus

Risk factors were distributed as reported in Table 4. There were no statistically

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Selected Abbreviations and Acronyms

3. Nencini P, Inzitari D, Baruffi MC, Fratiglioni L, Gagliardi R, Benvenuti L,

9. Headache Classification Committee of the International Headache Society.

12. Guidetti D, Baratti M, Zucco R, Greco G, Terenziani S, Vescovini E, Sabadini R,

17. Adams H Jr, Butler M, Biller J, Gilbert J. Nonhemorrhagic cerebral infarction in

28. Lechat P, Mas JL, Lascault G, Loron P, Theard M, Klimczac M, Drobinski G,

Hanrath P. Comparison of transcranial contrast Doppler sonography and

35. Barinagarrementeria F, Cantu-Brito C, Aurora P, Izaguirre R. Prothrombotic

37. Montalban J, Rio J, Khamastha M, Davalos A, Codina M, Swana GT,

45. Lidegaard O. Oral contraception and risk of a cerebral thromboembolic

47. Brandt T, Hausser I, Orbeck E, Muller-Kuppers M, Anton-Lamprecht I, Hacke

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