Stroke. 2006;37:2159-2161
Published online before print July 6, 2006,
doi: 10.1161/01.STR.0000231645.22128.ab
(Stroke. 2006;37:2159.)
© 2006 American Heart Association, Inc.
Embolic Lesion Pattern in Stroke Patients With Patent Foramen Ovale Compared With Patients Lacking an Embolic Source
Marek Jauss, MD;
Tiemo Wessels, MD;
Susan Trittmacher, MD;
Jens Allendörfer, MD
Manfred Kaps, MD
From the Departments of Neurology (M.J., T.W., J.A., M.K.) and Neuroradiology (S.T.), University of Giessen, Giessen, Germany.
Correspondence to Marek Jauss, MD, Department of Neurology, University of Giessen, Am Steg 14, D-35385 Giessen, Germany. E-mail marek.jauss{at}neuro.med.uni-giessen.de
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Abstract
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Background and Purpose Multiple acute ischemic lesions
on diffusion-weighted magnetic resonance imaging (DWI-MRI) are
thought to be of embolic origin. However, in several patients
with multiple ischemic lesions on DWI-MRI, no embolic source
was detected, despite a thorough clinical work-up. Stroke etiology
in such cases is then classified as cryptogenic. In other patients,
a potential embolic source is limited to a patent foramen ovale
(PFO) that may act as an embolic source of unsure relevance.
We therefore examined the prevalence of the multiple-lesion
pattern in patients with cryptogenic stroke compared with patients
with PFO.
Methods We screened 650 stroke patients by DWI-MRI. For the subsequent evaluation, we excluded patients with a cardiac embolic source other than PFO, symptomatic carotid artery disease, and other apparent stroke causes, such as dissection or vasculitis, and patients whose diagnostic work-up was incomplete. For the remaining 106 patients, we found DWI lesions in 73, who were subjected to further evaluation.
Results There were no differences in the occurrence of the multiple-lesion pattern in patients with cryptogenic stroke compared with patients with PFO, either for the entire group or for the subgroup of young stroke patients who were <50 years old. Patients with PFO showed a significantly higher incidence of multiple lesions in the posterior circulation.
Conclusions The multiple-lesion pattern on DWI-MRI is not uncommon, even when extensive testing does not reveal any embolic source. Therefore, it is not possible to discriminate between cryptogenic stroke and stroke from an assumed paradoxical embolism.
Key Words: foramen ovale, patent magnetic resonance imaging, diffusion-weighted
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Introduction
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In many patients, multiple acute ischemic lesions on diffusion-weighted,
magnetic resonance imaging (DWI-MRI) are associated with detection
of an embolic source, such as a ventricular thrombus or atrial
fibrillation.
1 However, in some patients, despite a thorough
examination including transesophageal echocardiography (TEE)
and Holter ECG, no embolic source can be revealed. In other
patients, the only pathological finding is a patent foramen
ovale (PFO) that might act as an embolic source of unsure relevance.
The aim of this study was to compare the prevalence of the multiple
ischemic lesion pattern in patients with cryptogenic stroke
and patients with PFO and to examine whether the distribution
of ischemic lesions differs between these groups. In addition,
we examined whether recurrent infarctions on DWI-MRI, as has
been described to occur in

40% of acute stroke patients,
2 are
more common in patients with PFO than in patients who lack an
embolic source.
DWI-MRI already has had a substantial impact on early stroke diagnosis and therapy. In contrast to computed tomography and MRI without DWI, detection of lesions in the first hours after the onset of clinical symptoms is possible with DWI. Furthermore, DWI is superior in detecting very small ischemic lesions because of the high signal-to-noise ratio and its capacity of differentiating between chronic and acute lesions.3 Small, clinically "silent" lesions may influence the diagnosis of stroke subtype in ischemic stroke when multiple lesions are detected on DWI.4 The presence of multiple ischemic lesions suggests embolism from the heart or the aortic arch or, if confined to 1 vascular territory, from stenosis of an extracoronary or intracranial large artery. Multiple infarcts in >1 vascular territory, especially bilateral lesions, strongly argue for a proximal source or a systemic cause.1 These may be also present when caused by a lacunar syndrome on clinical grounds that an arteriosclerotic stroke etiology is assumed.5
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Patients and Methods
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We examined 650 stroke patients who underwent DWI-MRI and who
were consecutively admitted to the Department of Neurology,
University Hospital, Giessen, Germany, during a 3-year period.
For the subsequent evaluation, we excluded patients with carotid
stenosis (n=118), other apparent stroke causes such as dissection
or vasculitis (n=20), or an apparent embolic source (atrial
fibrillation, n=105; aortal plaques, n=44; dilated ventricle,
n=40; other cardiac embolic sources, n=41). One hundred seventy-seven
patients were excluded because the work-up data were incomplete.
For the remaining 106 patients, we found DWI lesions in 73 patients
who were subjected to further evaluation. In the group with
negative MRI findings, the PFO incidence was 36% (n=12) compared
with 49% PFO-positive patients in the patient group with DWI
lesions on MRI.
Patients underwent DWI-MRI usually within 72 hours of symptom onset by a 1.5-T whole-body scanner (General Electric) with echoplanar imaging data capability. The study protocol has been published previously.6 Because the aim of DWI-MRI was to disclose stroke etiology rather than to search for early infarct signs, the time between onset of symptoms and MRI scan was at least 8 hours. All MRI-scans were assessed by both a neuroradiologist and a neurologist who were blinded to the clinical findings.
Ischemic DWI lesions were classified as (1) single lesions, (2) multiple lesions (see the Figure) in 1 vascular territory (anterior or posterior circulation), and (3) multiple lesions in >1 vascular territory, as suggested in previous studies wherein multiple lesions were considered to be of embolic origin.1,4,7 The presence of cardiac right-to-left shunting was examined by TEE with an intravenous contrast agent (Echovist) and confirmed by a transcranial Doppler test for right-to-left shunt.8 Only patients with positive results on both tests were considered as having a right-to-left shunt on the cardiac level. Statistical analysis was performed with Fishers exact test.

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Two representative DWI-MRI slices for a patient with PFO and multiple lesions in the posterior territory.
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Results
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The mean age of the study patients was 53.1±16.1 (range,
18 to 88) years, and 28 patients (38%) were female. The time
from onset of symptoms to MRI examination was 2.2±1.4
(range, 1 to 8) days.
There was no significant difference in the occurrence of the multiple ischemic lesion pattern in patients with cryptogenic stroke compared with patients with PFO, either for the entire group or for the subgroup of young stroke patients who were
50 years old. Patients with the multiple ischemic lesion pattern showed significantly more lesions in the posterior circulation (the Table), with a positive prediction value for PFO in cases of multiple emboli in the posterior circulation of 0.99 (0.51 to 1), a specificity of 0.99 (0.88 to 1), and a sensitivity that was low, 0.20 (0.07 to 0.35).
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Frequency and Distribution of Lesion Pattern, Distribution of Multiple Lesions, and the Presence of Recurrent Lesions on DWI MRI in Patients With PFO Compared With Those Lacking an Apparent Embolic Source
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Discussion
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We report on a selected group of patients from a cohort of stroke
patients who often present with the problem of determined stroke
etiology. The failure to disclose an embolic source of stroke
in patients with an embolic stroke pattern by MRI is not uncommon,
despite extensive testing. Therefore, the multiple ischemic
lesion pattern is not limited to patients with stroke and PFO.
Only in young patients (

50 years) was there a remarkably high
positive predictive value of 75% for the presence of PFO in
cases of the multiple ischemic lesion pattern on MRI. The observation
that stroke due to paradoxical embolism affects mainly the posterior
circulation is supported by a single-photon emission computed
tomography study and is possibly a specific feature of paradoxical
embolism.
9
The limitations of this study are possible bias due to patient selection for DWI-MRI, because cooperation of the patient is required for this examination, and a possible bias in patient selection for TEE, because TEE, though part of our stroke work-up program, was performed as an invasive procedure only in patients who would have been expected to derive a possible therapeutic consequence.
In conclusion, the multiple ischemic lesion pattern is common in PFO patients, but it can also be demonstrated in a subgroup of patients in whom no obvious source of embolic stroke can be demonstrated. The multiple ischemic lesion pattern in the posterior circulation is associated with the presence of PFO.
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Acknowledgments
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Disclosures
None.
Received November 6, 2005;
revision received March 7, 2006;
accepted March 21, 2006.
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References
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