Examining the Lacunar Hypothesis With Diffusion and

Perfusion Magnetic Resonance Imaging

Richard P. Gerraty, MD, FRACP; Mark W. Parsons, FRACP; P. Alan Barber, PhD, FRACP;
David G. Darby, PhD, FRACP; Patricia M. Desmond, MSc, FRACR;
Brian M. Tress, MD, FRACR; Stephen M. Davis, MD, FRACP

Background—The clinical diagnosis of subcortical cerebral infarction is inaccurate for lesion location and pathogenesis.
Clinically suspected small perforating artery occlusions may be embolic infarcts, with important implications for
investigation and treatment. New MRI techniques may allow more accurate determination of the stroke mechanism soon
after admission.
Methods—In a prospective series of 106 patients evaluated with acute diffusion-weighted MRI (DWI) and perfusion-
weighted MRI (PWI) within 24 hours of stroke, we enrolled 19 with a lacunar syndrome. On the basis of the topography,
DWI and PWI findings, and outcome T2 MRI, we determined whether the mechanism of infarction was single
perforating vessel occlusion or large artery embolism.
Results—Thirteen patients had pure motor stroke, 2 had ataxic hemiparesis, and 4 had sensorimotor stroke. Six patients
had lacunes on MRI, none with PWI lesions. Four patients had subcortical and distal cortical infarcts on DWI. Nine had
solitary restricted striatocapsular infarcts. Seven of these 9 had PWI studies, 5 with PWI lesions. The presence of a PWI
lesion reliably differentiated striatocapsular from lacunar infarction for solitary small subcortical infarcts (P⫽0.03).
Conclusion—DWI and PWI altered the final diagnosis of infarct pathogenesis from small perforating artery occlusion to
large artery embolism in 13 of 19 patients presenting with lacunar syndromes. Lacunes cannot be reliably diagnosed on
clinical grounds. (Stroke. 2002;33:2019-2024.)
Key Words: cerebral infarction 䡲 magnetic resonance imaging 䡲 stroke

T he lacunar hypothesis states that particular clinical syn-

dromes are caused by small infarcts of the brain, owing
to single perforating artery occlusion, the result of local
microatheroma and thrombosis of that single vessel.1 The
pathological foundations for our understanding of lacunes in
the modern era were laid by Fisher,2 and subsequent clinico-
radiological studies with computed tomography (CT) have
supported to some extent the validity of the lacunar hypoth-
esis.3–5 Clinical diagnosis is inaccurate, however, particularly
for pure motor stroke,6 and the lacunar hypothesis has been
questioned by many authors, most notably Millikan and
Futrell,7,8 who point out the considerable evidence in favor of
embolism accounting for small deep infarcts in many pa-
tients. The possible role of embolism in patients suspected of
having lacunar infarction is important from the point of view
of investigation and treatment.
Recent studies using diffusion-weighted MRI (DWI) have
shown that some patients with suspected subcortical infarcts
have cortical lesions,9 and multiple small subcortical infarcts
on DWI indicate an embolic source of cerebral ischemia.10 –13
In contrast to multiple DWI abnormalities, the stroke etiology
in patients with solitary small DWI lesions is more difficult to
determine. One early study of DWI in subcortical infarction
found a solitary lesion consistent with a lacune in 37 of 39
patients,14 but in a later report by the same group lesions
extending beyond lacunar sites were described in 24 of 43
patients enrolled with a lacunar syndrome. Only 1 of these
was a cortical lesion, and many of the nonlacunar type
involved the capsule and an adjacent structure. No MRI
images were included, and volumetric analysis was not
performed.15
Volumetric measurements alone, in which the upper vol-
ume limit for a lacune should be ⬇1.8⫻103 mm3,16 will not
necessarily differentiate acute lacunar from striatocapsular
infarction as there may be some overlap in their dimensions
on DWI. Given the embolic mechanism of striatocapsular
infarcts, perfusion imaging may provide valuable supplemen-
tary information.17 In particular, a perfusion defect larger than
the DWI lesion might not be expected from single perforator
occlusion, even when the DWI lesion is of lacunar dimen-
sions. This is not to say that there is no perfusion lesion
accompanying a lacune, but that hypoperfusion of one single

Received September 4, 2001; final revision received February 27, 2002; accepted April 8, 2002.
From the Departments of Neurology (R.P.G., M.W.P., P.A.B., D.G.D., S.M.D.) and Radiology (P.M.D., B.M.T.), Royal Melbourne Hospital, and
Department of Medicine, St. Vincent’s Hospital (R.P.G.), University of Melbourne, Victoria, Australia.
Correspondence to Richard P. Gerraty, MD, FRACP, Department of Neurology, Royal Melbourne Hospital, Parkville 3050, Melbourne, Victoria,
Australia. E-mail rgerraty@medstv.unimelb.edu.au
© 2002 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000020841.74704.5B

2019
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
2020 Stroke August 2002
perforating artery may be beneath the resolution of current
MRI perfusion imaging methods. There are no studies ad-
dressing this issue. Combined DWI and magnetic resonance
angiography (MRA) has been shown to improve diagnostic
accuracy with respect to stroke subtype in one recent study.13
There is no study looking at the combination of diffusion
and perfusion imaging in suspected lacunar infarction. We
aimed to assess the influence of combined DWI and
perfusion-weighted MRI (PWI) on the final diagnosis of
infarct pathogenesis in patients admitted with lacunar
syndromes.
Methods
Patients
Patients with a sudden-onset focal neurological deficit consistent
with hemispheric ischemic stroke were recruited prospectively from
the Stroke Service of the Royal Melbourne Hospital where 400
patients with acute stroke are admitted each year. The period of the
recruitment was 50 months. Stroke onset was defined as the last time
the patient was known to be without a neurological deficit. Patients
were excluded if they had cerebral hemorrhage, preexisting signifi-
cant nonischemic neurological deficits (including dementia or extra-
pyramidal disease), or a history of prior stroke that would hamper
interpretation of clinical and radiological data. There were no age,
gender, or handedness exclusions. The study was performed with the
approval of the Clinical Research and Ethics Committee at our
institution, and written informed consent was obtained from the
patient or next of kin. All patients had MRI studies within 24 hours
of stroke onset, and all had outcome T2-weighted MRI studies at 3
months. All clinical assessments were performed by a neurologist or
neurology resident without knowledge of the imaging results. The
clinical diagnosis was made in the emergency department by either
the neurologist or neurology resident trained in the differentiation of
subcortical from cortical infarcts. No formal assessment of interob-
server agreement was made between any 2 examiners, but the
diagnosis of all patients was reviewed by the admitting stroke
neurologist who either assessed the patient in the emergency depart-
ment or reviewed the patient within 24 hours of admission. Later
information from neuroimaging or nonacute neurological or neuro-
psychological assessments did not affect the acute clinical infarct
classification.
All MRI scans were obtained using a 1.5-T echo-planar imaging
(EPI)– equipped whole-body scanner (Signa Horizon SR 120; Gen-
eral Electric) using a standard protocol as previously described.17–20
Diffusion Imaging
DWI was obtained using a multislice, single-shot spin-echo EPI
sequence. Slice thickness was 6 mm with a 1-mm gap, with the
number of slices set to include the whole brain (average of 15).
Matrix size was 256⫻128 (128⫻128 for the first 7 patients), field of
view was 40⫻20 cm, and TR/TE was 6000/100 ms (TE was 75 ms
for the first 5 patients). Diffusion gradient strength was varied
between 0 and 22 mT/m, resulting in 5 b values of increasing
magnitude from 0 up to 1200 s/mm2. The diffusion gradient was
applied in 3 orthogonal directions (x, y, and z), and an average of
these measurements was calculated to give the trace of the diffusion
tensor.
The protocol was changed after the first 22 patients, with TR/TE
of 10 000/100 ms, and the diffusion gradient strength varied so that
there were 3 b values of increasing magnitude from 0 to 1000 s/mm2.
The diffusion sensitizing gradient was applied in 6 directions (xy, xz,
yz, x, y, and z); however, for the purposes of this study, analyses were
performed from the average of the measurements taken in the x, y,
and z orthogonal directions.
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
Perfusion Imaging
Perfusion images were obtained using dynamic first-pass bolus
tracking of gadolinium diethylenetriamine penta-acetic acid (Gd-
DTPA) using an EPI spin-echo sequence with a TR/TE of 2000/70
ms. The Gd-DTPA bolus (0.2 mmol/kg) was administered by manual
intravenous injection over ⬇5 seconds via a large-bore cannula in the
antecubital fossa in the first 18 patients recruited, and subsequently
an EPI gradient-echo sequence with a TR/TE of 2000/70 ms was
used with the Gd-DTPA bolus (0.1 mmol/kg) being administered by
a power injector (Spectris MR injector, MEDRAD) at a rate of 5
mL/s. A total of 10 slices were obtained, with a slice thickness of
6 mm with a 1-mm gap, a matrix of 256⫻128, and a field of view of
40⫻20 cm. Images were obtained at 40 time points per slice, with a
total imaging time of 1 minute 21 seconds. The concentration-time
curve obtained was processed on a voxel-by-voxel basis, allowing
determination of an observed or relative mean transit time map,
where the relative mean transit time is related to the sum of the true
mean transit time plus the injection time.
Magnetic Resonance Angiography
Phase-contrast MRA was performed as previously described.19
Postprocessing of MR images was performed using customized
software based on commercial image analysis applications (Ad-
vanced Visualization Systems) using an Indigo R10000 workstation
(Silicon Graphics Inc). DWI volumes were measured using the
maximum diffusion sensitivity isotropic image because this showed
the greatest contrast between the hyperintense infarct and the
surrounding tissue. The edge of the DWI or PWI lesion was
identified visually and regions of interest were outlined using a
manual pixelwise method. The area of the region of interest was
multiplied by the slice thickness plus the interslice gap and then
summed. Analyses used the average of 2 measurements taken on
separate occasions by 2 neurologists trained in the technique and
blinded to clinical data. Intra- and interobserver agreement was high
with variability ⬍10%.
Infarct Subtype Definition
The lacunar syndromes were the following: (1) pure motor hemipa-
resis, weakness of face, arm, and leg without sensory symptoms or
signs and without evidence of dysphasia; (2) pure sensory stroke,
hemianesthesia without cortical signs or weakness; (3) sensorimotor
stroke, a combination of the above; (4) ataxic hemiparesis, ataxia of
the arm and leg with ataxia out of proportion to the weakness; and (5)
dysarthria clumsy hand syndrome.21
The final infarct pathogenesis was determined on the basis of a
combination of the infarct topography on acute DWI and the final
outcome T2 volumes. The acute DWI reliably revealed recent
infarction location and number, and differentiated any old ischemic
lesions from those to be analyzed. Where there were multiple lesions
on DWI, the infarct was attributed to embolism. Solitary infarcts
were classified as lacunes, attributable to single perforating artery
occlusion, if the 3-month T2 MRI volume was ⬍1.8⫻103 mm3. This
cutoff volume was based on the usual definition of an upper diameter
limit of 15 mm for lacunes,22 assuming lacunes are spherical.16
Infarct topography was deemed consistent with a lacune for spherical
or spheroidal infarcts of the above dimensions, and including
cylindrical infarcts of the pons such as paramedian perforating artery
territory infarcts. Infarcts including the putamen, caudate, and
capsule were classified as striatocapsular infarcts. Smaller lenticu-
lostriate artery territory infarcts larger than 1.8⫻103 mm3 on 3-month
T2 MRI were classified as restricted striatocapsular infarcts.23 Such
infarcts are most often lateral striatocapsular, and most obviously
affect the posterior one-third or one-half of the putamen. The
outcome T2 MRI provided the volumes for the final diagnostic
classification, as the traditional size criteria are taken from patho-
logical studies that examined mostly old infarcts. Furthermore, it is
known that acute DWI lesions with PWI deficits expand in the first
72 hours,18,24 whereas lacunes have been shown to shrink slightly on
outcome T2 follow-up, 1 to 5 months later.9
 Gerraty et al Diffusion and Perfusion MRI in Lacunar Stroke 2021

TABLE 1. Clinical and MRI Volume Data

Time to MRI DWI PWI Outcome T2
Patient Sex Age Clinical Infarct Description Risk Factors (hours) ⫻103 mm3 ⫻103 mm3 ⫻103 mm3
1 F 77 PMS SC Nil 22 2.7 5.1 2.5
2 M 58 PMS SC, two parts AF 5.5 1.2 2.9 3.1
3 F 67 PMS Lac Put HT, DM 10 0.8 0 0.7
4 M 70 PMS SC HT, IHD, smoker 23 2.0 0 2.1
5 M 71 PMS Lac Caps HT 10.5 0.5 0 0.3
6 M 72 PMS SC Smoker, CCF 5 6.1 NA 3.5
7 M 63 PMS MB⫹Thal⫹Occip Smoker, HT 13 12.2 12.5 13.2
8 F 71 PMS SC DM 5 1.5 0 1.9
9 M 54 PMS SC Nil 5 2.9 4.9 4.6
10 F 61 PMS SC HT, ICA stenosis 6 5.2 NA 70
11 F 75 AH Lac Caps HT, DM 22 0.3 0 0.3
12 F 78 SMS Lac Thal HT 5 0.7 0 0.4
13 F 78 PMS Lac Pons Hyperchol 8 0.4 0 0.8
14 F 79 SMS Thal⫹Occip AF, HT 3 1.5 3.5 3.0
15 M 87 AH Lac Put DM 12 1.1 0 0.9
16 M 53 PMS SC Smoker, HT 3 2.5 1.0 1.9
17 F 74 SMS SC⫹Parietal Nil 3 8.1 9.3 9.0
18 F 59 PMS SC⫹Parietal⫹Insula HT, dilated LA, PFO 5 5.5 2.5 5.2
19 F 54 SMS SC HT, Smoker 11 1.0 2.7 2.3
PMS indicates pure motor stroke; SC, striatocapsular infarct; Lac, lacune; Put, putamen; Caps, capsular; MB, midbrain; Thal, thalamus; Occip,
occipital; AH, ataxic hemiparesis; AF, atrial fibrillation; HT, hypertension; CCF, cardiac failure; DM, diabetes; ICA, internal carotid artery; Hyperchol,
hypercholesterolaemia; LA, left atrium; and PFO, patent foramen ovale.

Statistical Analysis
Figures expressed as means are appended ⫾SD. The Fisher exact test
was used for categorical variables. Results were considered signifi-
cant at P⬍0.05.
Results
Nineteen (18%) of 106 patients presented with typical lacunar
syndromes (Table 1). Five patients of 111 presenting within
24 hours with acute cerebral infarction had been excluded as
a result of previous stroke and residual neurological deficit.
There were 11 women and 8 men with mean age 68.5⫾9.9
years. Thirteen patients had pure motor stroke, 2 had ataxic
hemiparesis, and 4 had sensorimotor stroke. One patient with
pure motor hemiparesis had a contralateral sixth nerve palsy
as a result of a single perforating artery territory pontine
infarct (patient 13). This would be consistent with Fisher’s21
lacunar syndrome number 11 in the table included in his
review of lacunar infarcts. No patient had dysarthria clumsy
hand syndrome. The patient with the largest striatocapsular
infarct at presentation (patient 17) had no cortical signs on
routine bedside testing but was subsequently found to have
subtle inattention to formal neuropsychological tests of visual
function.
Four of the 19 patients had recognized sources of embo-
lism, atrial fibrillation, carotid stenosis, and patent foramen
ovale, and all had striatocapsular or cortical infarction or
both, consistent with an embolic pathogenesis. None of the 6
patients with an MRI final diagnosis of lacunar infarction had
a recognized source of embolism. Eleven patients had a
history of hypertension, 4 of the 6 with lacunes and 7 of the
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
remaining 13 with embolic infarcts. One patient had had a
previous contralateral stroke caused by a lacune (patient 3,
Table 1).
There were 6 isolated subcortical infarcts with a final
diagnosis of lacunar infarction. The positive predictive value
of a clinical diagnosis of lacunar infarction in the 19 patients
was 32%. The average lacune volume on 3-month T2 MRI
was 0.57⫾0.27⫻103 mm3. Three other patients had acute
DWI lesion volumes ⬍1.8⫻103 mm3 but had subsequent
infarct expansion and final diagnoses of striatocapsular in-
farction (patients 2, 8, and 19; see Methods, Table 1, and
Figure 1. Six further patients had isolated restricted striato-
capsular infarction with acute DWI and outcome T2 volumes
⬎1.8⫻103 mm3. Four patients had both subcortical and
cortical infarction on acute DWI (Figure 2).
For the isolated solitary subcortical hemisphere infarcts,
there was a significant association between the presence of an
acute PWI lesion and a larger 3-month T2 infarct volume
(⬎1.8⫻103 mm3), consistent with restricted striatocapsular
infarction. Of the 7 patients with restricted striatocapsular
infarcts who had a PWI study, 5 had PWI lesions. Three of
these patients with PWI lesions larger than DWI had acute
DWI lesion volumes ⬍1.8⫻103 mm3, but had subsequent
infarct expansion. No patient with lacunar infarction as the
final diagnosis had an acute PWI deficit (P⫽0.03, Fisher’s
exact test; see Table 2.) Acute PWI lesions were present in all
4 patients with cortical infarcts. The MRA did not show
occlusion of the middle cerebral artery (MCA) or posterior
circulation arteries in any of the 19 cases.
2022 Stroke August 2002
Figure 1. Patient 2. Top, Acute DWI showing a bifid infarct
topography but with volume within lacunar limits. Middle, Acute
PWI lesion (arrows). Bottom, day 4 DWI showing expansion of
the infarct to dimensions and topography of a restricted striato-
capsular infarction. h indicates hours; d, days.
Discussion
This is the first report detailing the role of PWI in determi-
nation of the pathogenesis of infarction in patients presenting
with lacunar syndromes. Of 19 patients with clinical presen-
tations typical of lacunar infarction, 13 had MRI findings not
consistent with lacunar infarction as a result of occlusion of a
single perforating vessel. This conclusion was most obvious
when multiple DWI lesions were demonstrated within a large
artery territory. In the MCA territory this was typically a
simultaneous small striatocapsular infarct and a distal small
cortical infarct. This pattern is most likely to be due to
thrombus in the MCA, occluding the origins of a number of
lenticulostriate penetrating arteries, with subsequent fragmen-
tation and distal cortical branch occlusion. Embolism is
usually the cause of such proximal thrombotic MCA occlu-
sions.25–27 This series of lacunar syndrome patients may not
be representative of patients encountered routinely in an
Figure 2. Patient 18. Top, Acute DWI showing striatocapsular
and cortical infarction (arrow). Middle, Acute PWI. Bottom, DWI
at 72 hours. h indicates hours; d, days.
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
TABLE 2. PWI Lesion Frequency in the Two Hemisphere
Infarct Subtypes for Solitary Lesions
PWI⫹ PWI⫺
Lacune 0 5
Striatocapsular 5 2
P⫽0.03 (Fisher exact test, one tailed).
PWI⫹ indicates PWI lesion present; PWI⫺, PWI lesion not present.
emergency department, given the small sample taken from
⬎800 stroke admissions, but the percentage of lacunar
presentations within this larger MRI series (18%) is consis-
tent with many prospective registries of stroke subtype. One
previous series has described cortical infarcts in 2 of 23
patients presenting with lacunar syndromes,9 but another
group found only 1 cortical infarct in 43 patients with lacunar
syndromes.15 The early clinical assessment in our study may
have accounted for missing subtle signs of dysfunction of
cortical modalities, but although there is good evidence that
stroke subtype definition within 12 hours is less accurate than
at a later time point,28 –30 the very small cortical infarcts seen
on DWI in the 4 patients with combined cortical and
subcortical infarcts were not likely to be clinically detectable.
This early misdiagnosis is certainly relevant, however, to the
larger striatocapsular infarcts (see below).
Solitary infarcts in the lenticulostriate distribution, larger
than lacunes on acute DWI, constituted restricted striatocap-
sular infarcts (see Methods). The clear elucidation of the
topography and mechanism of striatocapsular infarction oc-
curred only in the CT era.25–27 They are typically comma
shaped and large enough to include the caudate head, puta-
men, and intervening internal capsule, dwarfing the typical
lacune with dimensions on the order of 45⫻40⫻20 mm.25
However, smaller lesions do occur. Fisher’s “giant lacunes,”
infarcts ⬎10 mm in diameter,2 were probably striatocapsular
infarcts for the most part.23,31 In the only formal subcortical
infarct classification so far proposed, size was not deemed the
only determinant of lacunes and striatocapsular infarcts,
limited forms of which were allowed to occur.22 In one CT
study of pure motor hemiparesis, a subset of the lesions were
clearly striatocapsular infarcts.32 In such cases misclassified
as lacunes, early recanalization of the occluded MCA has
been postulated as the explanation for the brief or inapparent
cortical dysfunction that is typical of large striatocapsular
infarcts.23 A restricted striatocapsular infarct involving the
posterior putamen is depicted in cartoon form (Reference 33,
Figure 1, panel 1) in a transcranial Doppler study of MCA
embolic occlusion, and a pathological specimen (Reference
23, Figure 12.1) in an important series of striatocapsular
infarcts, all typical of infarcts seen regularly not only on MRI
but also on CT in routine clinical practice. Such infarcts are
not lacunes and could not be accounted for by single
perforating artery occlusion. In a series of 43 patients pres-
enting with lacunar syndromes,15 9 patients had infarction of
at least 2 striatocapsular elements, most commonly posterior
limb of internal capsule and putamen. Without seeing the
infarct topography they encountered, one could only specu-
late as to whether they were seeing similar types of infarct.
 Gerraty et al
In the acute stage then (⬍24 hours), DWI alone may not be
able to differentiate lacunes from restricted striatocapsular
infarcts. Although none of the infarcts with a final diagnosis
of lacune had a PWI lesion, 3 patients had acute infarcts of
lacunar dimensions on DWI but with a larger acute PWI
deficit (patients 2, 14, and 19; see Figure 1). All 3 infarcts
expanded to lesions larger than lacunes at 3 months. For small
acute DWI lesions, the presence of a larger acute PWI deficit
may be a reliable determinant of an embolic mechanism of
cerebral infarction on initial MRI studies soon after the onset
of stroke. In 1 patient (patient 16, Table 1), the 3-hour
diffusion lesion of 2.5⫻103 mm3 had a smaller PWI lesion of
1.0⫻103 mm3 and the outcome lesion shrank to an outcome
T2 volume of 1.9⫻103 mm3. The lack of expansion may have
related to early reperfusion and the resolution of acute
infarction edema.
In the patient just discussed and in patients 4, 8, and 19, the
volumes of the outcome lesions were certainly close enough
to the stated volume cutoff of 1.8⫻103 mm3 that they may
actually have been lacunes rather than smaller restricted
striatocapsular infarcts due to embolism. This is particularly
so for patients 4 and 8, considering that neither of them had
a PWI lesion. The absence of a PWI lesion in these and the
lacunar infarcts is likely to relate to the resolution of the
technique, inasmuch as it is likely that there would be a
region of hypoperfusion associated with even the smallest
infarction.
None of the 19 patients had occlusion of the MCA or other
cerebral artery on MRI. This is likely to be one of the factors
giving rise to the milder strokes in these patients; the
striatocapsular patients must at some point before assessment
have had MCA embolic occlusion, but spontaneous recana-
lization has spared them from large territorial infarction and
even from large striatocapsular infarction.23
The average lacune volume was 0.57⫻103 mm3, as has
been found by others,9 and this indicates an average infarct
diameter of ⬇10 mm. Fisher2 said that it may be pointless to
set an absolute limit for the size of a lacune, but emphasized
that those ⬎10 mm in diameter were unusually large. The
average lacune volume in this and the other DWI study of
lacunes with volumetry9 is larger than Fisher’s pathological
studies indicated. His early work related mainly to asymp-
tomatic lacunes, however, and these are smaller than symp-
tomatic lacunes. In the subcortical infarction classification
proposed by Donnan et al,22 the authors pointed clearly to a
consideration of mechanism as being just as important as a
determination of size in the final diagnosis of an infarct. The
topographical pattern and size of infarction can be determined
acutely by DWI, but the supplementary information provided
by PWI may help clarify the mechanism and help differenti-
ate a restricted striatocapsular infarct due to MCA embolism
from a lacune due to single perforating artery occlusion. The
present study includes few subjects, and the implications
regarding the value of PWI are preliminary only and will need
to be explored in a larger prospective study of patients with
lacunar syndromes.
Combined DWI and PWI findings in acute stroke patients
further challenge the lacunar hypothesis7 when applied to the
diagnosis of individual patients in clinical practice.13 The
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
Diffusion and Perfusion MRI in Lacunar Stroke 2023
decision to more intensively investigate patients with cerebral
infarction is usually prompted by the early clinical signs of
cortical involvement, likely to indicate an embolic etiology.
This study shows that basing investigation on such purely
clinical findings may not be justified. It has been reported that
there is a benefit of carotid endarterectomy in patients with
tight carotid stenosis and suspected lacunar infarction.34
Recently aortic arch atheroma has been found to be an
independent risk factor for lacunar infarction, but its signifi-
cance for infarct mechanism is unknown.35 In both these
studies, and all earlier CT-based studies of lacunar infarction,
there is doubt about the uniformity of the case material. It is
possible that an admixture of lacunes, restricted striatocapsu-
lar infarcts, small embolic posterior circulation infarcts, and
other small infarcts with an embolic etiology constitute even
the most carefully chosen clinical set of “lacunar” infarcts.
Two other recent DWI studies suggest this.9,15 With the
possibility of occult cardiac embolism due to intermittent
atrial fibrillation, and with the emergence of other proximal
pathologies as significant potential sources of embolism,36,37
decisions about further investigation should not necessarily
be based solely on clinical bedside examination for cortical
signs. Further prospective studies of patients with lacunar
syndromes are needed to assess the routine clinical implica-
tions of this study, but for patients with lacunar syndromes
acute diffusion and perhaps perfusion MRI may be an
important modality for obtaining an early accurate diagnosis
of the infarct type and mechanism.
Acknowledgments
This study was supported by the National Health and Medical
Research Council (M.W.P. and P.A.B.), the National Stroke Foun-
dation, and the Neurological Foundation of New Zealand V.J. Chap-
man Research Fellowship (P.A.B.).
References
1. Bamford JM, Warlow CP. Evolution and testing of the lacunar
hypothesis. Stroke. 1988;19:1074 –1082.
2. Fisher CM. Lacunes: small, deep cerebral infarcts. Neurology. 1965;15:
774 –784.
3. Boiten J, Lodder J. Lacunar infarcts: pathogenesis and validity of the
clinical syndromes. Stroke. 1991;22:1374 –1378.
4. Landi G, Cella E, Boccardi E, Musicco M. Lacunar versus non-lacunar
infarcts: pathogenetic and prognostic differences. J Neurol Neurosurg
Psychiatry. 1992;55:441– 445.
5. You R, McNeil JJ, O’Malley HM, Davis SM, Donnan GA. Risk factors
for lacunar infarction syndromes. Neurology. 1995;45:1483–1487.
6. Gan R, Sacco RL, Kargman DE, Roberts JK, Boden-Albala B, Gu Q.
Testing the validity of the lacunar hypothesis: the Northern Manhattan
Stroke Study experience. Neurology. 1997;48:1204 –1211.
7. Millikan C, Futrell N. The fallacy of the lacune hypothesis. Stroke.
1990;21:1251–1257.
8. Millikan CH. About lacunes. In: Donnan G, Norrving B, Bamford J,
Bogousslavsky J, eds. Lacunar and Other Subcortical Infarctions. New
York: Oxford University Press Inc; 1995:24 –28.
9. Lindgren A, Staaf G, Geijer B, Brockstedt S, Stahlberg F, Holtas S,
Norrving B. Clinical lacunar syndromes as predictors of lacunar infarcts:
a comparison of acute clinical lacunar syndromes and findings on
diffusion-weighted MRI. Acta Neurol Scand. 2000;101:128 –134.
10. Ay H, Oliveira-Filho J, Buonanno FS, Ezzeddine M, Schaefer PW,
Rordorf G, Schwamm LH, Gonzalez RG, Koroshetz WJ. Diffusion-
weighted imaging identifies a subset of lacunar infarction associated with
embolic source. Stroke. 1999;30:2644 –2650.
11. Baird AE, Lovblad KO, Schlaug G, Edelman RR, Warach S. Multiple
acute stroke syndrome: marker of embolic disease? Neurology. 2000;54:
674 – 678.
2024 Stroke August 2002
12. Roh J-K, Kang D-W, Lee S-H, Yoon B-W, Chang K-H. Significance of
acute multiple brain infarction on diffusion-weighted imaging. Stroke.
2000;31:688 – 694.
13. Lee LJ, Kidwell CS, Alger J, Starkman S, Saver JL. Impact on stroke
subtype diagnosis of early diffusion-weighted magnetic resonance
imaging and magnetic resonance angiography. Stroke. 2000;31:
1081–1089.
14. Singer MB, Chong J, Lu D, Schonewille WJ, Tuhrim S, Atlas SW.
Diffusion-weighted MRI in acute subcortical infarction. Stroke. 1998;29:
133–136.
15. Schonewille WJ, Tuhrim S, Singer MB, Atlas SW. Diffusion-weighted
MRI in acute lacunar syndromes: a clinical-radiological correlation study.
Stroke. 1999;30:2066 –2069.
16. Gerraty RP, Parsons MW, Barber PA, Darby DG, Davis SM. The volume
of lacunes. Stroke. 2001;32:1937–1938.
17. Darby DG, Barber PA, Gerraty RP, Desmond PM, Yang Q, Parsons M,
Li T, Tress BM, Davis SM. Pathophysiological topography of acute
ischemia by combined diffusion-weighted and perfusion MRI. Stroke.
1999;30:2043–2052.
18. Barber PA, Darby DG, Desmond PM, Yang Q, Gerraty RP, Jolley D,
Donnan GA, Tress BM, Davis SM. Prediction of stroke outcome with
echoplanar perfusion- and diffusion-weighted MRI. Neurology. 1998;51:
418 – 426.
19. Barber PA, Davis SM, Darby DG, Desmond PM, Gerraty RP, Yang Q,
Jolley D, Donnan GA, Tress BM. Absent middle cerebral artery flow
predicts the presence and evolution of the ischemic penumbra. Neurology.
1999;52:1125–1132.
20. Barber PA, Darby DG, Desmond PM, Gerraty RP, Yang Q, Li T, Jolley
D, Donnan GA, Tress BM, Davis SM. Identification of major ischemic
change: diffusion-weighted imaging versus computed tomography.
Stroke. 1999;30:2059 –2065.
21. Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982;32:
871– 876.
22. Donnan GA, Norrving B, Bamford JM, Bogousslavsky J. Subcortical
infarction: classification and terminology. Cerebrovasc Dis. 1993;3:
248 –251.
23. Weiller C. Striatocapsular infarcts. In: Donnan G, Norrving B, Bamford
J, Bogousslavsky J, eds. Lacunar and Other Subcortical Infarctions. New
York: Oxford University Press Inc; 1995:103–116.
24. Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad KO, Edelman RR,
Warach S. Enlargement of human cerebral ischemic lesion volumes
Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015
measured by diffusion-weighted magnetic resonance imaging. Ann
Neurol. 1997;41:581–589.
25. Bladin PF, Berkovic SF. Striatocapsular infarction: large infarcts in the
lenticulostriate arterial territory. Neurology. 1984;34:1423–1430.
26. Weiller C, Ringelstein EB, Reiche W, Thron A, Buell U. The large
striatocapsular infarct: a clinical and pathophysiological entity. Arch
Neurol. 1990;47:1085–1091.
27. Donnan GA, Bladin PF, Berkovic SF, Longley WA, Saling MM. The
stroke syndrome of striatocapsular infarction. Brain. 1991;114:51–70.
28. Toni D, Del Duca R, Fiorelli M, Sacchetti ML, Bastianello S, Giubilei F,
Martinazzo C, Argentino C. Pure motor hemiparesis and sensorimotor
stroke: accuracy of very early clinical diagnosis of lacunar strokes.
Stroke. 1994;25:92–96.
29. Toni D, Fiorelli M, De Michele M, Bastianello S, Sacchetti ML, Montinaro
E, Zanette EM, Argentino C. Clinical and prognostic correlates of stroke
subtype misdiagnosis within 12 hours from onset. Stroke. 1995;26:
1837–1840.
30. Toni D, Iweins F, von Kummer R, Busse O, Bogousslavsky J, Falcou A,
Lesaffre E, Lenzi GL. Identification of lacunar infarcts before
thrombolysis in the ECASS I study. Neurology. 2000;54:684 – 688.
31. Mohr JP. Lacunes. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, eds.
Stroke: Pathophysiology, Diagnosis, and Management. 2nd ed. New
York: Churchill Livingstone; 1992:539 –560.
32. Rascol A, Clanet M, Manelfe C, Guiraud B, Bonafe A. Pure motor
hemiplegia: CT study of 30 cases. Stroke. 1982;13:11–17.
33. Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte PE, Thron A.
Type and extent of hemispheric brain infarctions and clinical outcome in
early and delayed middle cerebral artery recanalization. Neurology. 1992;
42:289 –298.
34. Inzitari D, Eliasziw M, Sharpe BL, Fox AJ, Barnett HJ. Risk factors and
outcome of patients with carotid artery stenosis presenting with lacunar
stroke: North American Symptomatic Carotid Endarterectomy Trial
Group. Neurology. 2000;54:660 – 666.
35. Kazui S, Levi CR, Jones EF, Quang L, Calafiore P, Donnan GA. Risk
factors for lacunar stroke: a case-control transesophageal echocardio-
graphic study. Neurology. 2000;54:1385–1387.
36. Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G,
Chauvel C, Touboul PJ, Bousser MG. Atherosclerotic disease of the
aortic arch and the risk of ischemic stroke. N Engl J Med. 1994;331:
1474 –1479.
37. Jones EF, Kalman JM, Calafiore P, Tonkin AM, Donnan GA. Proximal
aortic atheroma: an independent risk factor for cerebral ischemia. Stroke.
1995;26:218 –224.
Examining the Lacunar Hypothesis With Diffusion and Perfusion Magnetic Resonance
Imaging
Richard P. Gerraty, Mark W. Parsons, P. Alan Barber, David G. Darby, Patricia M. Desmond,
Brian M. Tress and Stephen M. Davis

Stroke. 2002;33:2019-2024
doi: 10.1161/01.STR.0000020841.74704.5B
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2002 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/33/8/2019

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.

Reprints: Information about reprints can be found online at:

http://www.lww.com/reprints

Subscriptions: Information about subscribing to Stroke is online at:

http://stroke.ahajournals.org//subscriptions/

Downloaded from http://stroke.ahajournals.org/ by guest on December 13, 2015