Identification of Embolic Stroke Patterns by

Diffusion-Weighted MRI in Clinically Defined Lacunar

Stroke Syndromes
Tiemo Wessels, MD; Carina Röttger, MD; Marek Jauss, MD;
Manfred Kaps, MD; Horst Traupe, MD; Erwin Stolz, MD

Background—A number of clinical syndromes describing the presentation of deep brain infarcts are called lacunar
syndromes resulting from small vessel occlusion (SVO). To verify the reliability of the clinical diagnosis “lacunar
syndrome,” the value was investigated with diffusion-weighted MRI (DWI).
Methods and Results—A total of 73 patients (mean age 66 years; range 35 to 83 years) with sudden onset of a classical
lacunar syndrome were enrolled. On the basis of the DWI findings, patients were divided into 3 groups: group 1, single
subcortical lesion (⬍15-mm lesion; 43 patients; 59%); group 2, large (ⱖ15 mm) or scattered lesions in 1 vascular
territory (16 patients; 22%); and group 3, multiple lesions in multiple vascular territories (14 patients; 19%). A stroke
mechanism other than SVO could be identified in 17 (23%) patients. Cardiac work-up revealed a cardiac embolic source
in 8 patients (11%). Duplex sonography revealed symptomatic stenosis in 9 patients (12%). Based on the work-up
information, 29 patients (40%) were found to have a potential cause of stroke other than SVO. A significant correlation
with ⬎1 single lesion on DWI-MRI and a clinical proven embolic source was observed (P⫽0.002). In 9 patients with
MRI suspicious for a pathomechanism other than SVO, no embolic source was found.
Conclusions—The use of DWI-MRI improves the accuracy of the subtype diagnosis of stroke. Inaccuracy has to be
expected in approximately one third if lacunar diagnosis is based on clinical and computed tomography findings. Most
of these “false-positive” cases are attributable to large artery or cardiogenic embolic stroke. (Stroke. 2005;36:757-761.)
Key Words: clinical syndrome 䡲 lacunar stroke 䡲 magnetic resonance imaging 䡲 stroke
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I n the early half of the 19th century, the first postmortem

reports on lacunar stroke were published.1 Fisher2,3 was the
first to describe the clinical “lacunar stroke syndrome.” The
Patients and Methods
Over 1.5 years, 382 consecutive patients with ischemic stroke were
screened and 73 patients were recruited for this study. Inclusion
term “lacunar infarction” for deep brain ischemia was coined. criterion was the presentation with an acute lacunar stroke syn-
drome2,5,7 (DCHS, PMS, PSS, SMS, AH, or HACP) assessed by a
Following Fisher’s definition,2,3 lacunar strokes are still board-certified neurologist unaware of the imaging findings. Exclu-
defined as small brain lesions (0.2 to 15 mm3) caused by sion criteria were “cortical symptoms” such as aphasia, apraxia, and
occlusion of the deep brain perforating arteries and resulting hemianopia, as well as seizures and disturbed consciousness. In all
in distinct clinical syndromes: dysarthria-clumsy hand syn- cases, the following stroke risk factors were recorded: hypertension,
diabetes, hyperlipidemia, hyperhomocysteinemia, peripheral vascu-
drome (DCHS), pure motor stroke (PMS), pure sensory lar disease, smoking, previous transient ischemic attack or stroke,
stroke (PSS), sensorimotor stroke (SMS), ataxic hemiparesis coronary artery disease, and atrial fibrillation (AF). Criteria for AF
(AH), homolateral ataxia, and crural paresis (HACP).2 The were known history of permanent or paroxysmal AF or newly
underlying mechanism is thought to be local thrombosis diagnosed permanent or paroxysmal AF on 24-hour Holter-ECG.
All patients received an extracranial and transcranial color-coded
caused by microatheroma and lipohyalinosis.2– 6 Because of
duplex ultrasound examination. Transthoracic echocardiography
the clear clinical definition of lacunar strokes and the pre- (TTE) and 24-hour Holter-ECG monitoring was obtained in every
sumed pathophysiology, a frequently found notion is to patient. Additional transesophageal echocardiography was per-
concentrate on treatment of underlying risk factors and not to formed if TTE, Holter-ECG and duplex sonography of the extracra-
extensively search for embolic sources in these patients. nial and intracranial vessels did not show evidence for cardiogenic or
large artery embolism in 48 (66%) patients.
In this study, we evaluated the yield of diffusion-weighted
MRI (DWI) in patients with a clinically defined acute lacunar Computed Tomography Imaging
stroke syndrome in detecting embolic stroke patterns, which In all cases, intracranial hemorrhage was excluded by a computed
might alter treatment decisions. tomography (CT) scan on admission. Brain CT scans (performed on

Received October 20, 2004; final revision received December 22, 2004; accepted January 10, 2005.
From the Departments of Neurology (T.W., C.R., M.J., M.K., E.S.), and Neuroradiology (H.T.), Justus-Liebig-University of Giessen, Germany.
Correspondence to Tiemo Wessels, Medizinisches Zentrum für Neurologie und Neurochirurgie Neurologische Klinik und Poliklinki, Am Steg 14,
35393 Giessen, Germany. E-mail [email protected]
© 2005 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000158908.48022.d7

757
 758 Stroke April 2005

a Somatom Plus CT system; Siemens) were evaluated for cerebral an embolic source was not found despite duplex sonography
infarction and leukoariosis. The finding of leukoariosis in 7 brain of the extracranial and intracranial vessels, cardiac diagnos-
regions was graded by CT: absent, mild (in at least 1 of 7 brain
tics, and MR angiography. Based on the work-up informa-
regions), or severe (present in all 7 brain regions), as suggested by
van Swieten et al.8 tion, 29 patients (40%) were found to have a potential cause
of stroke other than small vessel occlusive disease.
Magnetic Resonance Imaging
MRI was performed within 48 hours of symptom onset on a CT and MRI
1.5-Tesla whole body scanner (General Electrics) equipped with No clearly symptomatic acute lesions were identified on
echo planar imaging data capability designed to obtain rapid diffu-
admission CT scan. CT showed no (18 patients; 25%), mild
sion images (repetition time 4657 ms; echo time 118 ms; matrix
128⫻128; gradients of b-values 0, 500, and 1000 s/mm2). The (37 patients; 50%), and severe leukoariosis (18 patients;
apparent diffusion coefficients (ADCs) were calculated for each 25%). On DWI, 34 of the 51 patients (67%) had a single
pixel and composed to an ADC map. Time-of-flight magnetic hyperintense subcortical lesion with a diameter of ⱕ15 mm,
resonance (MR) angiography was performed with a spoiled gradient consistent with the clinically assumed lacunar stroke; and in
echo sequence (2D TOF; flip angle 50°; bandwidth 15.63; slice
thickness 1.5 mm; field of view 26 cm). Images were reconstructed 9 patients (17%), a pontine infarct was found (group 1). Eight
3-dimensionally using a maximum intensity projection. All MRI patients (16%) showed a subcortical single lesion of ⱖ15-mm
scans were assessed by a neuroradiologist and a neurologist unaware diameter (group 2). In groups 1 and 2, all DWI lesions were
of the clinical findings. On the basis of the DWI findings, the patients located in a region appropriate for the clinical symptoms.
were divided into 3 groups: (1) single subcortical lesion (diameter Based on the work-up information in 86% of all patients in
⬍15 mm); (2) large and scattered lesions in 1 vascular territory
(ⱖ15 mm; scattered small lesions ⬍15 mm or confluent scattered group 1, the assumed cause of stroke was small vessel
lesions ⱖ15 mm); and (3) multiple lesions in multiple vascular occlusive disease (P⬍0.0001).
territories as defined in recent studies.9,10 Group 3 consisted of 14 patients (Table; Figures 1 and 2).
The leukoariosis in 7 brain regions was graded by T2 MRI: absent, DWI discovered multiple hyperintense lesions in 1 vascular
mild (in ⱖ1 of 7 brain regions) or severe (present in all 7 brain
territory in 7 (10%; group 2), and in ⬎1 territory in 14
regions), as suggested by van Swieten et al.8
patients (21%; group 3), consistent with an embolic stroke
Stroke Subtype pattern. In 13 patients (groups 2 and 3), a single cortical
To determine the stroke subtype, Trial of Org 10172 in Acute Stroke lesion (4 patients; 5%) and scattered or multiple lesion
Treatment (TOAST)11 classification criteria were used. The stroke patterns (9 patients; 12%) containing a cortical lesion were
subtype diagnosis was based on clinical, laboratory and imaging observed on DWI. The positive predictive value for the
data.
finding of a cortical lesion and an etiology other than SVO
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Statistical Analysis resulted in a moderate value of 0.69. The number of large

All numerical variables were expressed as mean⫾SD. The ␹ 2 test artery arterosclerosis and cardioembolism as underlying
and Fisher’s exact tests, if appropriate, were used to analyze the stroke reasons did not differ significantly among these
differences between patients with and without more than a single patients.
lesion on DWI-MRI. The Fisher exact test was used to compare the Agreement of 2 blinded and independent observers for
frequency of an identifiable mechanism between the patients with a
lacunar or embolic stroke mechanisms. Agreement of 2 observers for classification of the DWI pattern was excellent (ICC, 0.95;
classification of the DWI was analyzed using the intraclass correla- 95% CI, 0.76 to 0.99). Sensitivity of the initial clinical
tion coefficient (ICC). A level of P⬍0.05 was considered significant. classification for the actual presence of a lacunar stroke on
DWI was low (0.58). The presence of leukoariosis on initial
Results CT (mild 0.75; severe 0.65) as well as T2-weighted MRI
Clinical Variables (mild 0.76; severe 0.65) had low positive predictive values
The Table summarizes demographic data of the patient cohort for lacunar stroke (⬍15-mm subcortical ischemia) on DWI.
and a comparison of risk factors among groups 1 to 3. Mean
age was 66 (range 35 to 83) years. Cardiac work-up (echo- TOAST Classification
cardiography; 24-hour Holter-ECG) revealed a cardiac em- Based on the work-up information, 7 patients in group 1
bolic source in 8 patients (11%). AF was diagnosed as the (18%) were found to have a potential cause of stroke other
causal mechanism in 6 patients (8%), in 1 patient, a ventric- than small vessel occlusive disease. In 6 patients, cardiac
ular thrombus, and in another, a severe dilative cardiomyop- embolism and large artery disease were the assumed under-
athy was found. Duplex sonography of the extracranial and lying etiology.
intracranial vessels revealed a stenosis in 9 patients (12%). For group 2, SVO was the stroke etiology for 7 patients
Internal carotid artery stenosis was observed in 6 patients (44%), cardiac embolism was diagnosed in 3 patients (18%),
(8%), and in 2 patients, a high-grade basilar artery stenosis and large artery disease in 1 patient (7%). In 4 patients (25%)
was diagnosed. The ultrasound findings were proved by MR with scattered lesion patterns, no other stroke risk factor than
angiography in all patients. Two patients showed large aortic hypertension was found. As recommended by the guide-
plaques ⬎4 mm as a possible stroke mechanism. lines,11 these patients were not classified as SVO because of
A stroke mechanism other than small vessel occlusion the lesion pattern. Based on the work-up information, 11
(SVO) could be identified in 17 (23%) patients. In 9 patients, patients of the group with more than a single lesion (69%)
an embolism was assumed because of DWI-MRI with scat- were found to have a proven cause of stroke other than small
tered and large (group 2) and multiple lesions (group 3). But vessel occlusive disease (P⬍0.0001).
 Wessels et al The Value of DWI in Lacunar Syndromes 759

Imaging Characteristics and Clinical Findings

Total Group 1 Group 2 Group 3
Cohort (n⫽43) (n⫽16) (n⫽14) P Value*
Age (range) 63 (35–83) 64 (42–81) 67 (35–83) 70 (41–82) NS
Sex 0.024
Female (%) 31 (42) 13 11 7
Male (%) 42 (57) 30 5 7
Risk factors 0.89
HT (%) 64 (88) 36 (87) 15 (94) 13 (93)
DM (%) 22 (30) 12 (28) 6 (37%) 4 (29)
HC (%) 28 (38) 15 (39) 6 (37) 7 (50)
S (%) 15 (20) 7 (20) 2 (12) 6 (43)
HCYS (%) 12 (16) 7 (16) 2 (12) 3 (21)
Previous stroke/TIA (%) 22 (30) 12 (28) 4 (25) 6 (43)
Type of LC syndrome 0.11
PMS (%) 22 (30) 13 (30) 2 (12) 7 (50)
PSS (%) 6 (8) 4 (9) 2 (12) 0
SMS (%) 15 (20) 11 (25) 3 (18) 1 (7)
DCHS (%) 15 (20) 7 (16) 2 (13) 6 (43)
AHP (%) 8 (11) 4 (9) 4 (25) 0
HACP (%) 7 (10) 4 (9) 3 (19) 2 (14)
Embolic sources 0.002
AF (%) 6 (8) 1 (2) 2 (12) 3 (22)
Large artery stenosis (%) 9 (12) 4 (9) 1 (7) 4 (29)
Other embolic source (%) 2 (3) 0 1 (7) 1 (7)
Stroke subtype ⬍0.001
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SVO (%) 44 (60) 37 (86) 7 (44) 0

CE (%) 8 (11) 1 (2) 3 (18) 4 (29)
OTH (%) 11 (15) 3 (7) 4 (25) 4 (29)
LAA (%) 9 (12) 3 (7) 1 (7) 5 (36)
HT indicates hypertension; DM, diabetes mellitus; HC, hypercholesterolemia; TIA, transient
ischemic attack; S, smoking; HCYS, hyperhomocysteinemia; LAA, large artery arterosclerosis; CE,
cardioembolism; OTH, stroke of undetermined etiology.
*Fisher exact test.

For group 3, a stroke mechanism could be identified in 9 The clinical management and therapy decisions are influ-
(65%) of these patients. Cardiac work-up (echocardiography; enced by stroke subtype and etiology. Therefore, early
24-hour Holter-ECG) revealed a cardiac embolic source in 4 classification is of substantial clinical value.12,13 Long-term
patients (29%). AF was diagnosed as the causal mechanism in therapy and prevention differ significantly among distinct
3 patients (21%), and in 1 patient, a ventricular thrombus was stroke subtypes. DWI is a highly sensitive and specific
found. Duplex sonography of the extracranial and intracranial technique for use in the early diagnosis of acute stroke.14,15
vessels revealed symptomatic internal carotid artery stenosis DWI provides improved information about embolic lesion
in 5 patients (36%). Altogether, in 9 patients of group 3 pattern compared with CT scan.16,17 This is supported by
(65%), a cause of stroke other than small vessel occlusive recent studies using DWI that have shown that patients with
disease was diagnosed based on the extensive work-up assumed subcortical infarcts on DWI may have cortical
(P⬍0.0001). Further significant differences in clinical pre- lesions18 and multiple small deep brain infarcts, indicating an
sentation among the 3 subgroups were not observed. embolic source.9,10,19 Multiple lesions on DWI support an
embolic etiology.10,20,21
Discussion Those patients with multiple infarctions on DWI were
In this study of 73 patients presenting with a classical lacunar more likely to harbor an identifiable stroke mechanism than
syndrome, 21 patients had embolic stroke patterns with more those with a single lacunar infarction.15 However, whether
than a single lesion on DWI, and 14 patients showed multiple multiple DWI lesions in different vascular territories occur-
infarcts in different vascular territories. This highlights that ring simultaneously are caused by embolic showers or recur-
the clinical presentation alone has a low predictive value for rent emboli remains unknown. Other possible explanations
evaluation of the actual stroke type. are diffuse thrombotic or inflammatory processes that lead to
 760 Stroke April 2005

emboli for a combined finding of subcortical and cortical

lesions was confirmed by autoptic studies.24,25 Soloway and
Aronson described in 1964 the finding of cholesterol crystals
within the leptomeningeal cortical and cerebellar branches
and in the deep brain perforating arteries. Vessels with a
diameter of 14 ␮m were loaded with cholesterol emboli.
These autopsy findings suggest that if a deep brain artery is
occluded by a small embolus, more of such emboli may be
expected in different brain vascular territories. The infarction
in the territory of a penetrating artery can be explained by its
lack of leptomeningeal collateral pathways and a greater
susceptibility to ischemia. The finding of multiple acute
infarcts in different vascular territories strongly indicates
Figure 1. This patient presented with a lacunar syndrome embolism. However, whether DWI lesions are caused by
(SMS). CT scan showed no pathology. Axial DWI-MRI demon- recurrent emboli or embolic showers is still unclear. Using
strates hyperintense signals in the left anterior internal capsula well-accepted criteria for grading of leukoariosis by CT scan
and in the left cerebral peduncle. An embolic source was not
and T2 MRI does not result in acceptable positive predictive
found.
values for the presence of a small, single lesion on DWI.
Our data and the results of other studies18,19,23 indicate that
multiple SVOs. Chowdhury et al investigated 10 patients with
relying entirely on the clinical presentation as lacunar syn-
multiple subcortical lesions in a recent study. A definite
drome may put patients at risk when search of embolic
embolic source was identified in only 1 patient. The authors
sources is omitted. Inaccuracy has to be expected in about one
assumed a generalized intrinsic process affecting many small
third if lacunar diagnosis is based on clinical and CT findings.
cerebral vessels contemporaneously, causing multiple acute
Most of these false-positive cases are attributable to large
small subcortical infarcts.22
artery or cardiogenic embolic stroke. Of course, on the other
In a number of studies, different rates for the detection of
hand, coexisting lacunar infarctions in patients with athero-
embolic sources in patients with multiple DWI lesions were
sclerotic or cardiogenic embolic sources are possible. For
identified.9,19,21 Symptomatic extracranial arteriosclerosis or
patients with lacunar syndromes, DWI may be an important
major cardioembolic sources were found in patients with
modality to obtain the accurate diagnosis and stroke subtype
lacunar infarctions, but 2 to 3⫻ less frequently than among
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and should prompt the physician to search for an underlying

patients with cortical infarctions.19,23 This is supported by our
embolic source.
findings in which large artery embolism was found as the
underlying stroke mechanism in 6 of 22 patients (27%) with
more than a single infarct but only in 3 of 51 patients (6%)
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