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1. A case series of young stroke in Rome
M. Rasuraa
, A. Spallonia
, M. Ferraria
, S. De Castrob
, R. Patellaa
, F. Di Lisia
and M. Becciaa
a
Department of Neurological Sciences, II Faculty of Medicine, University of Rome ÔLa SapienzaÕ; and b
Department of Cardiovascular and
Respiratory Sciences, I Faculty of Medicine ÔLa SapienzaÕ University, Policlinico Umberto I, Rome, Italy
Keywords:
etiology, ischemic stroke,
young
Received 17 September 2004
Accepted 1 February 2005
In this hospital case series study we enrolled 394 consecutive ischemic stroke pa-
tients aged 14–47 years, all of whom were submitted to a diagnostic protocol. We
evaluated the incidence of cerebral ischemia in young adults, as well as the risk
factors and the etiopathogenesis of this pathology. Modified diagnostic criteria
adopted from the TOAST and Baltimore–Washington Cooperative Young Stroke
Study were used for the etiologic classification.The crude annual incidence rate was
8.8/100 000 (95% CI 7.7–9.9), which is in keeping with the rates reported in
comparable registries. Risk factors were distributed as follows: smoking in 56% of
patients, hypertension in 23%, dyslipidemia in 15%, migraine in 26%, and diabetes
mellitus in 2%. Oral contraceptives were being taken by 38% of the women en-
rolled. The etiology of stroke in the patients was as follows: cardioembolism in
34%, atherothrombosis in 12%, non-atherosclerotic vasculopathies in 14% (inclu-
ding arterial dissection in 12%), other determined causes in 13%, lacunar stroke in
2.5%, migraine in 1%, and undetermined causes in 24%.Despite its biased samp-
ling frame, this large hospital case series, in which risk factor distribution and
etiopathogenesis were investigated, stresses the need for an adequate diagnostic
approach in young ischemic patients.
Introduction
Ischemic stroke in patients younger than 45 years of
age has been considered a relatively rare event,
accounting for <5% [1] of all cerebral infarctions in the
majority of studies, and few reporting figures exceeding
10% [2,3]. The age-specific incidence of stroke among
individuals under 45 years has been investigated by
community and hospital surveys in various geographic
areas.
Young people who suffer a stroke may live with their
disability longer than older stroke patients, and are thus
subject to a lifetime of medical complications which
determine high socioeconomic costs. The etiologic
spectrum in older patients and young patients differs
considerably, with the main causes being atherosclerosis
in the former, and cardioembolism and arterial dissec-
tion in the latter [4–6]. Moreover, no cause has been
found in up to one-third of young patients. Advances in
technology, including transesophageal echocardio-
graphic investigation, magnetic resonance angiography
(MRA) of intra- and extracranial vessels, and new
biochemical assays, have revealed new potential causes
of ischemic stroke, such as patent foramen ovale (PFO),
arterial dissection, and coagulopathies.
The aim of the study was to investigate the etiology
and incidence of ischemic stroke in a young population,
and compare our results with those of previous reports.
Methods
In this hospital case series study we prospectively
evaluated, from 1992 to 2001, 394 consecutive patients
(187 males and 207 females, mean age 36.4 years), aged
14–47 years, admitted to the Neurological Department
of the Policlinico Umberto I, University of Rome ÔLa
SapienzaÕ, for a first-ever acute ischemic stroke. The
Policlinico Umberto I was, at that time, the only hos-
pital in Rome with a Stroke Unit, and is the hospital to
which the majority of stroke patients are referred in this
city. In particular, this hospital contained the ÔResearch
Group of Stroke in the YoungÕ we belong to, which led
to other hospitals in Rome contacting us when a stroke
was diagnosed in young patients.
For the purposes of this study, we only enrolled
patients resident in this area. We chose the age limit of
14–47 years because they had been defined as such in
the original study design in 1992. We excluded episodes
of transient global amnesia, loss of consciousness,
vertigo, drop attacks, and migraine with aura without
Correspondence: Dr Mario Beccia, Neurologia, II Facoltà di
Medicina e Chirurgia Policlinico S. Andrea, Università di Roma
ÔLa SapienzaÕ, Via di Grottarossa n1035 00189 Rome, Italy
(tel.: +390680345774; fax: +3906822184; e-mail: mario.beccia@
uniroma1.it).
146 2006 EFNS
European Journal of Neurology 2006, 13: 146–152

2. subsequent neurologic signs. All the patients gave their
informed written consent; the study was approved by
our local ethical committee.
The protocol included a detailed medical history of
all the patients, as well as a cardiac and neurologic
evaluation, and standard laboratory blood tests: red
and white cell counts, hematocrit, platelet count,
fibrinogen, activated partial thromboplastine time,
erythrocyte sedimentation, concentration of blood
glucose, serum creatinine, urea nitrogen, electrolytes,
total cholesterol, high density lipoprotein cholesterol,
triglycerides, protein C, protein S, antithrombin III, C3,
C4, activated protein C resistance, lupus anticoagulant
(LAC), anticardiolipin antibodies (aCL), antinuclear
antibodies, anti-DNA, antiextractable nuclear antigen,
antineutrophil cytoplasm antibodies, and serologic test
for AIDS and syphilis. We also performed genetic tests
for coagulative factors, such as the G20210A mutation
in the factor II (prothrombin) gene in 158 patients and
factor V Leiden in 149 patients.
In addition, all the patients, even those with bad
clinical conditions, were submitted to an electrocardi-
ography, chest X-ray, carotid Doppler sonography and
transcranial Doppler, CT scan, and/or magnetic res-
onance imaging, and, in selected cases, MRA or cer-
ebral digital subtraction angiography.
All the subjects underwent transthoracic echocardi-
ography (TTE), while transesophageal contrast echo-
cardiography (TEE) was performed in 232 patients
following the advent of this examination. In selected
cases, such as patients with PFO, duplex ultrasound
was performed to investigate possible deep vein
thrombosis in the lower limbs.
Cerebrospinal fluid was tested in selected cases (24
patients) in order to exclude other diagnoses.
The following cerebrovascular risk factors were
considered: arterial hypertension, diabetes mellitus,
hypercholesterolemia, hypertriglyceridemia, family his-
tory of cardio- and cerebrovascular disease (in first-
degree relatives alone), cigarette smoking, alcohol and
drug abuse, previous history of migraine with and
without aura, and oral contraceptive use.
Hypertension was considered to be present when the
patient had previously been diagnosed as hypertensive
by a clinician, or when systolic blood pressure was
‡140 mmHg and/or diastolic blood pressure was
‡90 mmHG on two different occasions measured at
least 2 weeks after the acute stage. Diabetes mellitus
was diagnosed according to the National Institutes of
Health criteria [7]. Current cigarette smoking was de-
fined as a risk factor when a subject had smoked 10
cigarettes per day for more than 6 months before the
stroke. Alcohol consumption was regarded as a risk
factor when a subject had regularly consumed ‡30 g of
alcohol per day or ‡210 g per week for more than
6 months before the stroke. Hyperlipidemia was de-
fined as a risk factor when the fasting blood cholesterol
level was ‡200 mg/dl and/or the triglyceride level was
‡150 mg/dL. Migraine was defined according to the
International Classification of Headache Disorders [8].
Oral contraceptives were defined as a risk factor when a
subject had taken such contraceptives during the
6 months before the stroke.
The patients were further classified under the fol-
lowing seven categories on the basis of the modified
diagnostic criteria adopted from the TOAST [9]and
Baltimore [10]classification system adapted for stroke in
the young.
1 Atherosclerotic vasculopathy: probable – ipsilateral
intracranial or extracranial disease by angiogram or
non-invasive tests showing a hemodynamically signi-
ficant obstruction, 60% stenosis or a plaque with
an intraluminal clot; possible – ipsilateral intracranial
or extracranial disease by angiogram or non-invasive
tests showing any atherosclerotic disease.
2 Non-atherosclerotic vasculopathy: angiographic,
non-invasive or other evidence of arterial dissection,
vasculitis, fibromuscular dysplasia, or other specific
vasculopathy.
3 Lacunar infarct: lacunae not included in any other
category; small (15 mm) deep lesion on imaging
study, or normal imaging study and lacunar
syndrome.
4 Cardiac embolism: probable – atrial fibrillation, atrial
flutter, recent myocardial infarction (£6 weeks before
stroke), akinetic segment (a segment with no shor-
tening), cardiac thrombus, valvular vegetation, pros-
thetic heart valve, intracardiac tumors, dilated
cardiomyopathy, paradoxical embolism with deep
venous thrombosis, and cardiac malformations;
possible – remote myocardial infarction (‡6 weeks
before stroke) with no other abnormality, hypokinetic
segment (a segment with a regional shortening of
between 10 and 25%, while a normal segment has a
regional shortening of at least 25%), mitral annular
calcification, calcific aortic stenosis, PFO, atrial septal
aneurysm (ASA), atrial septal defect, aortic plaques
‡4 mm [11], and valvular strands.
5 Other determined causes: hematologic, immunologic
disorders, and coagulopathies such as thrombocyt-
hemia, polycythemia, deficiency of coagulation
inhibitors, antiphospholipid antibody, cerebral auto-
somal dominant arteriopathy with subcortical infa-
rcts and leukoencephalopathy (CADASIL), and
other documented causes of stroke not listed above.
6 Migrainous stroke: when the stroke occurred during
or immediately after a migraine attack, as defined by
the International Headache Society Criteria [8].
A case series of young stroke in Rome 147
2006 EFNS European Journal of Neurology 13, 146–152

3. 7 Undetermined: when no other probable or possible
diagnoses are satisfied.
Statistical analysis
Average crude incidence rates were calculated over the
study period. Ninety-five percent CI for incidence rates
were calculated assuming the Poisson distribution. All
the data used for comparison were standardized for age
and sex, using the indirect method, to the Italian pop-
ulation 2002. Student’s t-test was used to compare
group means.
Statistical analyses were performed using SPSS 11.0
for Windows (SPSS Inc., Chicago, IL, USA). The
ANOVA and chi-squared test were used to investigate
possible correlations between stroke subtypes and age,
gender, and risk factors. P 0.05 was considered sta-
tistically significant.
Results
During the study period, we identified 394 patients aged
14–47 years with clinical signs attributable to an acute
ischemic stroke. They comprised 187 males and 207
females, with a mean age of 36.4 years, standard devi-
ation 7.9 years.
In our hospital district, in 2002, there was a total
resident population of 800 000 individuals; 446 400
(56%) were 14–47 years of age. The proportion of
subjects in this age group was stable between 1992 and
2001. The crude annual incidence rate was 8.8/100 000
(95% C.I. 7.7–9.9) (Table 1). By dividing our popula-
tion into two age groups (14–24 and 25–47 years)
according to Italian Institute of Statistics [12] data, we
found that incidence rates increased with age, rising to
14/100 000 (95% C.I. 11.6–16.4) in patients older than
25 years of age. The incidence rates for stroke were 7.6
for males (95% CI 6–9.3) and 8.4 (95% CI 6.6–10.1) for
females. The incidence rate was 8.56/100 000 when
standardized according to age and sex to the 2002
Italian population [12]; this rate is within the range of
rates reported in comparable registries (Table 2)
[1,4,13–20].
The distribution of risk factors is shown in Table 3.
The most common risk factors were family history of
stroke (63%), cigarette smoking (56%), migraine
(26%), hypertension (23%), and hyperlipidemia (15%).
Oral contraceptives were being taken by 38% of the
women. In addition, the subjects were subdivided in
two age groups (14–35 and 35–47 years), as performed
in other young stroke registries [18]. Although con-
ventional atherosclerosis risk factors such as diabetes,
hypertension, hyperlipidemia, smoking, and alcohol
abuse were significantly more frequent (P 0.05) in
the older age group, there was no such difference be-
tween the two groups for family history, oral contra-
ceptive use, and obesity (Table 4). Migraine was more
frequent in women in the younger age group
(P 0.01).
When we compared the risk factor distribution and
etiologic stroke subtypes, we found a statistically sig-
nificant prevalence of hyperlipidemia in the Ôundeter-
minedÕ category (P 0.01) (Table 3). Family history,
smoking and hypertension were the most common risk
factors in the cardioembolic, atherosclerotic, and lac-
unar categories (Table 3).
Cardioembolism was detected in 133 patients (34%)
(Table 5). A probable cardiac source of emboli was
found in 23 patients, while possible embolic cardiac
abnormalities were detected in 110 patients. In the
former group, atrial fibrillation was present in four
patients (17%), followed by recent myocardial infarc-
tion in six (26%), PFO associated with deep venous
thrombosis in three (13%), atrial myxoma in two (8%),
and thrombus in the left atrium in one (4%). The most
frequent possible cardiac abnormality was right-to-left
cardiac shunt ascribable to PFO, which was detected in
60 of the 110 patients (54%) with a possible cardio-
embolic source. Isolated ASA was detected in 22 pa-
tients (20%), ASA associated with PFO in 16 patients
(14%). Aortic plaques were detected in five patients
(4.5%). The cardioembolic diagnostic subtype was
more frequent in the younger age group (41% vs. 29%,
P ¼ 0.016), with the most prevalent cardioembolic
source in this group being PFO (P 0.05). Aortic
plaques as ÔpossibleÕ cardiac abnormalities were present
in the older group alone.
An atherothrombotic etiology was found in 47 pa-
tients (12%). Probable atherosclerosis of extracranial or
intracranial arteries was detected in 38 patients (60–
70% stenosis in 18 patients, 47%; stenosis 70% in
two patients, 5%; occlusion in 18 patients, 47%), while
a possible extracranial and/or intracranial vasculopathy
Table 1 Incidence rates (per 100 000/year) according to sex and age,
in subjects aged 14–47 years in Rome
Age (years) No. of patients Rate 95% CI
Men
14–24 19 1.9 1–2.7
25–47 169 13.4 11–15.9
Women
14–24 19 2.2 1.2–3.2
25–47 187 14.6 12.1–17
Both
14–24 38 2.0 1.6–2.5
25–47 356 14.0 11.6–16.4
Total
14–47 394 8.8 7.7–9.9
148 M. Rasura et al.
2006 EFNS European Journal of Neurology 13, 146–152

4. (stenosis 50% or non-complicated plaque) was ob-
served in nine patients.
The main cause of non-atherosclerotic vasculopathy
was cervicocerebral arterial dissection (48 patients,
12%). Arterial dissection occurred spontaneously in 39
patients and was traumatic in nine. The carotid arteries
were involved in 39 patients, the vertebro-basilar system
in nine. The clinical picture was compatible with an
Table 2 Incidence rate (100 000/year) and distribution of ischemic stroke subtype in different countries
Country Age range (years) Patient no. Rate
Stroke subtype (%)
Lacunar ATS CE Mixed UE
Europe
Switzerland ( 4) 15–44 202 2.5 5.4 21.4 46.0 22.8
Sweden ( 1) 18–44 107 11.3 4.7 12.1 32.7 29.9 20.6
Italy
Florence ( 13) 15–44 47 3.4
Reggio Emilia ( 14) 15–44 17 8.0
L’Aquila ( 18) 0–44 51 5.8
Present study 14–47 394 8.8 2.5 12 33.7 28 23.8
North America
Canada ( 16) 15–45 356 8.0 6.0 14.0 28.0 44.0
USA ( 15) 18–44 116 3.0 16.0 14.0 44.0 23.0
Manhattan ( 19) 20–44 33 10.0 18.0 15.0 6.0 6.0 55.0
Far East
Taiwan ( 20) 15–45 241 6.8 22.4 7.9 19.5 24.5 25.7
Corea ( 17) 15–44 149 9.7 17.4 20.8 18.1 26.8 16.8
ATS, atherosclerotic vasculopathy; CE, cardiac embolism; mixed, other determined causes, non-atherosclerotic vasculopathies and migraine; UE,
undetermined.
Table 3 Risk factor distribution in each stroke subtype
ATS NAV Lacunar CE ODE Migraine UE
No. (%) 47 (12) 55 (14) 10 (2.5) 133 (33.7) 51 (13) 4 (1) 94 (23.8)
Age (years, mean ± SD) 37.8 ± 7.4 36.9 ± 9 38.3 ± 7.6 35.3 ± 7.6 35.2 ± 8.3 38.2 ± 8 37.2 ± 8
Male/Female (%) 49/51 60/40 50/50 45/55 55/45 25/75 39/61
Family history (%) 72.3 49 80 62.4 60.8 75 67
Diabetes (%) 4.2 1.8 0 3 2 0 2.1
Hypertension (%) 36.2 20 30 28 17.6 0 24.5
Smoking (%) 59.6 45.4 70 54.1 47 75 65
Alcohol abuse (%) 4.2 3.6 10 6 3.9 0 6.4
Obesity (%) 14.9 3.6 0 3.7 3.9 0 5.3
OC (%) 19.1 9 10 21.8 13.7 25 26.6
Migraine (%) 29.8 20 0 24 33.3 100 26.6
Dyslipidemia (%) 14.9 5.4 0 11.3 21.5 25 25.5*
ATS, atherosclerotic vasculopathy; NAV, non-atherosclerotic vasculopathies; CE, cardiac embolism; ODE, other determined etiologies; UE,
undetermined.
*P 0.01.
Table 4 Risk factor distribution for age and sex
14–35 (%) 36–47 (%)
TOT (394) (%)
Male (69) Female (90) All (159) Male (118) Female (117) All (235)
Family history 42 (60) 58 (64) 100 (63) 74 (63) 75 (64) 149 (63) 249 (63)
Diabetes 0 0 0 4 (3) 6 (5) 10 (4) 10 (2)
Hypertension 12 (17) 9 (10) 21 (13) 45 (38) 25 (21) 70 (30) 91 (23)
Smoking 36 (52) 42 (46) 78 (49) 81 (69) 62 (53) 143 (61) 221 (56)
Alcohol Abuse 3 (4) 0 3 (2) 15 (13) 3 (2) 18 (8) 21 (5)
Obesity 1 (1) 7 (8) 8 (5) 4 (3) 9 (8) 13 (5) 21 (5)
OC 0 34 (38) 34 (21) 0 44 (38) 44 (19) 78 (20)
Migraine 13 (19) 35 (39) 48 (30) 24 (20) 31 (26) 55 (23) 103 (26)
Dyslipidemia 6 (8) 7 (8) 13 (8) 26 (22) 22 (19) 48 (20) 61 (15)
A case series of young stroke in Rome 149
2006 EFNS European Journal of Neurology 13, 146–152

5. arteritis in only seven patients (1.8%) (three cases
diagnosed by capillaroscopy, one case with mesangio-
capillary glomerunephritis diagnosed by kidney biopsy,
one case of familial leukocytoclastic vasculitis, and two
cases with Neuro-Behçet).
Ten patients (2.5%) fulfilled the criteria for lacunar
infarct. The most common risk factors in this category
were family history (80%) smoking (70%), and hyper-
tension (30%).
Only four patients (1%) fulfilled the International
Headache Society criteria for a probable migraine-in-
duced stroke.
The Ôother determined causesÕ group (51 patients,
13%) comprised patients with autoimmune diseases
such as antiphospholipid antibody syndrome (36 pa-
tients) and LAC (eight patients), followed by those with
blood coagulation abnormalities [one polycythemia,
one sickle cell disease, one protein C and protein S
deficiency, one thrombocythemia, two patients with
CADASIL, and one with mitochondrial pathology
(Kearns-Sayre Syndrome)].
The etiology of cerebral infarction was, despite all the
investigations, not determined in 94 patients (24%).
Seventy-four of these patients presented more than two
risk factors, 16 only one, while the remaining four pa-
tients presented none.
In addition, 13 patients had a stroke during preg-
nancy or immediately postpartum.
In our study, we did not find any patient with two
probable higher priority diagnoses (e.g. atrial fibrilla-
tion and carotid stenosis 70%).
We found one factor II gene homozygous mutation
carrier and one factor V gene homozygous mutation
carrier; moreover, we found 18 factor II gene hetero-
zygous mutation carriers and 6 factor V gene hetero-
zygous mutation carriers. We did not find any
statistically significant association between these
mutations and the etiologic stroke subtypes.
We did not observe any cerebral ischemic event
related to drug abuse, AIDS, or syphilis.
Discussion
The present study comprises one of the largest reported
series of young adults with ischemic stroke investigated
by a group of physicians at a single medical center. The
few population- and hospital-based epidemiologic
studies that have been conducted have reported differ-
ent incidence rates, most probably as a result of dif-
ferences in the populations studied (Table 2). The low
number of young stroke cases means that large popu-
lation surveys are needed to overcome the restrictions
imposed by the wide confidence limits of these low
incidence rates. In Western countries, 5% of all
strokes occur in subjects 45 years of age [1], whereas
in developing countries the proportion of strokes in
these subjects rises to 20–30% [21].
Despite the biased sampling frame in our study, we
found an incidence rate comparable with those reported
in the literature. In Italy, the community-based registry
of stroke patients in the L’Aquila district reported an
incidence rate for cerebral infarction of 5.83/100 000.
Previous Italian data from a study conducted in Reggio
Emilia reported a similar rate. A recent study conduc-
ted in the Manhattan area (New York, USA) reported a
comparable rate for stroke (10/100 000). In keeping
with data in the literature, we also found that ischemic
stroke was even rarer in patients 24 years of age (2/
100 000). There was no difference in the incidence rates
between males and females in our series.
When we evaluated the distribution of risk factors
(Table 3), we found that hypertension, which is widely
considered to be a greater risk factor for stroke in the
general population than in young stroke patients, was
present in 23% of cases, which is similar to data
reported in the literature [1].
A positive family history of vascular events was
found in 63% of our patients, a figure which is higher
than that reported in other studies [20,22].
The prevalence of cigarette smoking was 56%; this
data is similar to that reported in the Taiwan Stroke
Registry [20] but higher than those reported in the
Northern Sweden Registry [1]and Italian National Re-
search Council Study Group on Stroke in the Young
[23].
A history of migraine was present in 26% of our
patients and was prevalent in females, which is in
keeping with data in previous studies [1,22].
In our series, embolism of cardiac origin accounts for
34% of the strokes, thus representing the most common
etiology. Other studies have reported a rate of the
cardioembolic stroke subtype which ranges from 6 to
33% (Table 2). The most frequent abnormality was
PFO, which was detected in 54% of possible cardio-
embolic patients. ASA was associated with PFO in 14%
Table 5 Etiology of cardioembolism (133 patients)
Probable (23) Possible (110)
Atrial fibrillation (4) PFO (60)
Recent myocardial infarct (6) ASA (22)
PFO + DVT (3) PFO + ASA (16)
Atrial septal defect (1) Aortic atheroma (5)
Thrombus (1) Aortic atheroma + PFO (2)
Atrial myxoma (2) Myocardial infarct (2)
Valvulopathy (4) Fibrin strands (3)
Cardiac malformations (2)
PFO, patent foramen ovale; DVT, deep venous thrombosis; ASA,
atrial septal aneurysm.
150 M. Rasura et al.
2006 EFNS European Journal of Neurology 13, 146–152

6. of patients, and isolated in 22% (Table 5). PFO is
reported to be present in a third of all stroke patients,
and is found in up to 40% of patients with ischemic
stroke who are younger than 55 years of age [24]. In our
study PFO was present in 40% of patients who
underwent TEE (93 of 232). Eighty-one of the 93 pa-
tients with PFO (87%) were classified under cardio-
embolic stroke, while the remainder fulfilled the criteria
for other diagnoses. Several studies with saline-contrast
TEE have suggested an increased prevalence of PFO in
patients with cerebral ischemia of undetermined origin
[25].
With regard to ASA, a meta-analysis of case–control
studies detected rates ranging from 2 to 17% for stroke,
4–25% for cryptogenetic stroke, 0.2–22% for known
stroke causes, and 0–15% for control subjects [26]. Our
results are in keeping with these findings.
We found only five patients (4.5%) with aortic pla-
ques ‡4 mm, all in the older subgroup of cardioembolic
patients. Although several studies have highlighted this
source of emboli as an important risk factor in patients
older than 60 years of age [1], few studies have pointed
to proximal aortic atheroma as a major cause of stroke
in the young [27,28].
In our series, we detected 12% of patients with
atherothrombotic infarction; the rates for this stroke
subgroup in the literature range from 5 to 21%
(Table 2).
The routine use of duplex ultrasonography and
MRA in our young acute ischemic stroke patients
resulted in the identification of 48 patients (12%) with
arterial dissection, a figure which reflects those reported
by other recent studies [29]. This finding stresses the
need to consider this diagnosis in all cases of stroke in
the young.
Anticardiolipin antibodies were found in 49 patients
(12%) and LAC in 16 patients (4%), although only 36
and eight of these patients, respectively, were classified
in the Ôother determined causesÕ group. The Taiwan
study found positive anticardiolipin antibodies in 7.6%
of the patients and positive LAC in 0.8% of the pa-
tients.
An inherited deficiency of coagulation inhibitors was
detected in 30 patients (7.5%): 12 with low antithrom-
bin III, nine with low protein S, five with low protein C,
and four patients with an inherited deficiency of both
protein C and protein S. Only one of these patients was
classified under Ôother determined causesÕ. This finding
suggests that a coagulation inhibitor deficiency or the
presence of anticardiolipin antibodies or LAC may be
associated with other major causes of stroke.
In the Ôundetermined causeÕ group (94 patients), it is
possible that some of the 33 patients who were only
submitted to a TTE might have been classified under
cardioembolic stroke, according to the TOAST-Balti-
more criteria, if a TEE and contrast echo had been
performed. In fact, Kristensen et al. [1] found that with
additional diagnostic information derived from ad-
vanced cardiac imaging, the proportion of patients with
an undetermined etiology could be reduced from 37 to
21%. Furthermore, if we consider only patients with
one or no risk factors as undetermined, the rate for this
category would drop from 24 to 5%. We could thus
classify patients with two or more than two risk factors
and with no other detectable causes of stroke under
Ôpresumed atheroscleroticÕ [23].
In conclusion, the proportion of different stroke
subtypes varies in different stroke registries; this may be
due to differences in the classification criteria used, the
methodologies adopted or to racial-ethnic differences in
populations. In young patients, a correct weighting of
the risk factors and adequate neurovascular investiga-
tions are needed [30]. The quantification of risk factors
that are likely to promote premature atherosclerosis is
therefore particularly important as those identified,
such as hypertension and cigarette smoking, are easily
modifiable and preventable.
Despite the biased sampling frame, the data extra-
polated from this hospital case series stress the need for
a thorough diagnostic work-up and the importance of
the latest examination techniques in young ischemic
patients.
Acknowledgements
We wish to thank Prof. Cesare Fieschi (head of the
First Neurological Clinic, University of Rome ÔLa Sa-
pienzaÕ) for his support and comments. The authors are
grateful to Mr Lewis Baker for his assistance in the
preparation of the manuscript.
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