990

Risk Factors and Clinical Manifestations of
Pathologically Verified Lacunar Infarctions
Mark H. Tuszynski, MD, Carol K. Petito, MD, and David E. Levy, MD
Review of 2,859 autopsy reports disclosed lacunar infarctions in 169 patients (6%). Review of
the charts of 167 of these patients revealed hypertension in 64%, diabetes in 34%, smoking in
46%, and no known risk factor for cerebrovascular disease in 18%. As many as 81% of the
patients with lacunes were asymptomatic. Symptomatic lacunes presented most commonly as
pure motor hemiparesis (31%), aphasia plus right hemiparesis (20%), or sensorimotor
dysfunction (11%); none presented as pure sensory stroke. These results suggest that the
spectrum of lacunar infarction is more heterogeneous than previously thought. Most lacunes are
asymptomatic, and the majority of symptomatic patients do not present with "classical"
lacunar syndromes. (Stroke 1989;20:990-999)

S

ubcortical infarcts are common causes of
stroke and represent up to 19% of all cerebral infarcts.1 Lacunar infarcts, the most
common form of subcortical infarcts, have been
defined by Fisher as small, deep cerebral infarcts
resulting from occlusion of small penetrating cerebral arteries.2 The etiology of lacunes is varied and
includes microvascular disease (lipohyalinosis and
microatheromata)3 as well as microemboli, microaneurysms, and arteritis.4-6 Hypertension is a risk
factor for lacunar infarction in approximately two
thirds of the patients with lacunes.1'7-9
A number of clinical syndromes have been
described in patients with lacunes. These syndromes include pure motor hemiparesis or hemisensory dysfunction, clumsy-hand dysarthria, ataxic
hemiparesis, movement disorders, and others.2-4'5'10
The relative frequency of these diverse clinical
presentations have not, however, been determined
in a large series of patients with pathologically
confirmed lacunes. Therefore, we reviewed the
clinical and postmortem records of all patients with
pathologically verified lacunar infarcts to examine
risk factors that may predispose to the development
of lacunes and the type and relative frequency of

From The New York Hospital-Cornell University Medical
Center, New York, New York.
Supported in part by National Institute of Aging Grant
AGO-0353A, National Institute of Neurological Disorders and
Stroke Grant NS-03346, The Robert Wood Johnson Foundation, the American Heart Association, and the New York
Heart Association.
Address for reprints: Mark H. Tuszynski, MD, Department of
Neurosciences, M-024, University of California, San Diego
School of Medicine, La Jolla, CA 92093.
Received December 5, 1988; accepted March 29, 1989.

the associated clinical dysfunction. Preliminary
results and a case report have been published.11-12
Subjects and Methods

Autopsy records at The New York Hospital from
1975 to 1985 were reviewed for reports of lacunes or
small subcortical infarcts sparing the overlying cortex. Infarcts that involved the cerebral cortex or
extensive areas of the subcortical white matter or
that were >2 cm in greatest diameter were excluded.
At the time of autopsy, the brain and spinal cord
were placed in formalin; after 2 weeks they were
serially sectioned at 1-cm intervals. After being
embedded in paraffin and stained with hematoxylin
and eosin, routine microscopic sections of the cerebral cortex, basal ganglia, hippocampus, cerebellum, brainstem, and spinal cord were examined.
Microscopic sections of a lacune were examined in
nearly all patients in whom such infarction was
suspected. The final autopsy report provided information about the cause of death, the size and
location of lacunes if present, and atherosclerosis in
the circle of Willis.
Etiologic mechanisms underlying lacunes were
evaluated by extensive pathologic investigation in a
subset of consecutive patients with lacunar infarcts
autopsied during the first 5 years of our study. The
microscopic brain slides of the basal ganglia were
reexamined for the presence of mild, moderate, or
severe medial hypertrophy, hyalinization, and dilatation in the intraparenchymal arteries and arterioles. Lipohyalinosis and Charcot-Bouchard aneurysms were classified as severe changes. The final
autopsy reports in this subset of patients were
reviewed for diagnoses of hypertension, atherosclerotic cardiovascular disease (ASCVD) in the absence

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Tuszynski et al Lacunar Stroke
TABLE 1.
Patients

Locations of 327 Pathologically Verified Lacunes in 169

Lacunes
Location
Basal ganglia
Internal capsule
Pons
Thalamus
Centrum semiovale
Claustrum
Midbrain
Hypothalamus

n
204
37
36
35
11
2
1
1

991

TABLE 2. Correlation Between Systemic Disease and Pathology of
Intraparenchymal Brain Vessels in 56 Patients With Lacunes
Verified at Autopsy

Pathologic changes of brain
vessels
62
11
11
11
3
0.6
0.3
0.3

of ulcerative plaques in the aorta or major vessels in
the neck or of mural thrombi in the left side of the
heart, ASCVD with ulcerative plaques in the aorta
or major vessels in the neck or with mural thrombi
in the left side of the heart, valvular heart disease,
embolic disease characterized by multiple systemic
and brain infarcts in the absence of hypertension
and ASCVD, and atherosclerosis in the circle of
Willis. The carotid bifurcation was not studied, and
only the intracranial portions of the internal carotid
and vertebral arteries were examined.
Clinical information for the patients with pathologically verified lacunes was obtained by chart
review and included age, sex, family history, smoking history, presence of diabetes, hypertension,
myocardial dysfunction, and neurologic signs and
symptoms. Information from neurologists was noted
separately. The clinical signs were compared with
the pathologic findings. The patients were divided
into five groups. Group A comprised patients with
symptoms and signs clearly attributable to a lacunar
infarct alone (for example, a hemiparesis contralateral to a lacune in the motor system with no
appropriately located cortical lesion). Group B consisted of patients with symptoms and signs clearly
attributable to cortical lesions (for example, hemiparesis associated with a contralateral cortical lesion
of the motor system but no contralateral lacune).
Group C patients had clinical symptoms that could
be attributed to either lacunes or cortical infarcts in
the same hemisphere. Group D contained patients
whose clinical symptoms had no apparent pathologic correlate (e.g., hemiparesis without contralatera! lacunes or cortical or brainstera infarcts).
Finally, group E consisted of asymptomatic patients
(no history of focal symptoms and nonfocal neurologic examinations) with lacunes at autopsy.
Results
Of 2,859 adult autopsies, 169 patients (6%) had
327 lacunes, an average of 1.9 lacunes per patient.
A single lacune was present in 46% of the patients,
two lacunes in 16%, and three or more lacunes in
38%. The anterior circulation contained 78% of the
lacunes and the posterior circulation 22% (Table 1).
Ninety-one percent of the infarcts for which size

Systemic disease

Normal
to mild
(71=27)

Moderate
(n=21)

Severe*
(n=8)

12

13

8

Hypertension
Alone
ASCVD
ASCVD+embolic source
Normotension
ASCVD
ASCVD+embolic source
Rheumatic heart disease
Embolic infarcts (? source)

3
5
4
15

3
1
9

1
2
5

8
6
5
2
2

0
2
4
1
1

0
0
0
0

ASCVD, atherosclerotic cardiovascular disease; embolic
sources include ulcerative plaques in ascending aorta or proximal neck vessels, or mural thrombi in left side of heart.
'Hypertensive and normotensive patients differ significantly
{x\ p<0.05) with respect to distribution of vascular pathology
but differences are not significant if those with severe pathologic
changes are omitted.

was specified were <1 cm in greatest diameter.
Coexistent but noncontiguous infarctions of the
cerebral cortex were present in 39% of the patients.
Atherosclerosis of the circle of Willis was moderate
to severe in 51% of the patients, mild in 27%, and
absent in 22%. Evidence at autopsy of acute or
remote myocardial infarction was found in 52% of
patients.
The subset of 56 consecutive patients with lacunar infarcts diagnosed at autopsy examination from
1975 through 1979 underwent more extensive evaluation of pathogenic mechanisms. Hypertension
was present in 59% of these patients and was
usually associated with ASCVD. The relative number of hypertensive patients with normal intraparenchymal vessels or with mild to moderate hyalinization or dilatation did not differ significantly from
that seen in normotensive patients with ASCVD
(/>>0.05); however, severe cerebral intraparenchymal vascular disease was significantly more common in hypertensive than in normotensive patients
with lacunes (p<0.05; Table 2). All eight patients
with severe cerebral intraparenchymal vascular disease among this subset of 56 patients were hypertensive and had marked hyalinization of the small
parenchymal arteries and arterioles; CharcotBouchard aneurysms were seen in three and lipohyalinosis in one. Since only one of the eight had
hypertension alone, the data suggest that the concurrence of hypertension with atherosclerosis may
predispose a cerebral vessel to develop severe
arterial and arteriolar pathology. At least 41% of the
56 patients in this subset may have had diseases
other than hypertension as the cause of their lacunes.
Rheumatic heart disease was the sole apparent
etiology in three patients, and embolic disease (from

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992

Stroke Vol 20, No 8, August 1989

TABLE 3. Risk Factors for Lacunes Verified at Autopsy in 167
Patients With Clinical Data
Risk factor

TABLE 4. 35 Lacunar Presentations in 32 Patients With Iscbemic
Events Attributable Solely to Lacunes

%

Hypertension
Diabetes
Smoker at time of stroke or death
Coronary artery disease
Family history of stroke
Family history of myocardial infarction
Hypertension, smoking, or diabetes
No risk factor

64
34
46
47
17
35
82
18

Hypertension, blood pressure of > 160/95 mm Hg or clinical
treatment for hypertension.

Total
(AT=35)
Symptoms/signs

n

%

n

%

Pure motor hemiparesis
Aphasia/right hemiparesis
Hemiparesis plus
Dysarthria

11

31
20
17

8
5

35
22
22

7

Change in LOC
Mutism
Unknown

2

2

2
1
1

2
1

Alone
Plus dysarthria
Extrapyramidal disease
Other
Total presentations

0
11

Sensorimotor dysfunction

possible nonbacterial thrombotic endocarditis not
persisting at autopsy) was the etiology in another
three patients with multiple systemic and brain
infarcts but without ASCVD or hypertension. In 17
patients, ASCVD was the sole etiology of lacunar
infarcts, secondary either to emboli from the aorta,
the proximal neck vessels, the unexamined portions
of the carotid or vertebral arteries, or secondary to
occlusive disease in the penetrating arteries at the
base of the brain. Nine of the 17 patients had either
ulcerative plaques in the aorta or its major proximal
branches in the neck or had mural thrombi overlying old myocardial infarcts as potential sources of
emboli. None of the 17 had occlusive ASCVD in the
appropriate artery at the base of the brain according
to the final autopsy descriptions.
Clinical data for the 10-year study period was
available for 167 (99%) of the 169 patients with
lacunes; the 167 patients had a total of 324 lacunes.
Neurologists evaluated 108 of the 167 patients (65%)
for symptoms referable to stroke or for other disorders including metabolic encephalopathy (18
patients), senile dementia of the Alzheimer's type
or parkinsonism (six patients), central nervous system metastases (five patients), and head trauma
(four patients). Hypertension was the most commonly noted risk factor among the 167 patients,
followed by coronary artery disease, cigarette smoking, and diabetes mellitus (Table 3). A family history of myocardial infarction (35%) was reported
more commonly than a family history of stroke
(17%). However, nearly one patient in five (18%)
lacked risk factors for cerebrovascular disease.
Eighty-four clinically evident ischemic cerebrovascular episodes occurred in 74 of these 167 patients
(44%), whereas the other 93 patients (56%) were
asymptomatic. Coexistent but noncontiguous cortical infarctions were present in 36 of the 74 symptomatic patients (49%). The sex ratio was 1.3:1
(male:female) and the mean age was 73.5 years.
The most frequent cause of death was acute myocardial infarction, present in 22% of these 167
patients; other forms of heart disease accounted for
another 5% of the deaths. Acute cerebrovascular
events caused 12% of the deaths, but most of these

Seen by
neurologists
(N=23)

3
1
1
6
35

17
3
1

3
17

1
0
23

4
0

N, number of patients; n, number of presentations; LOC, level
of consciousness; Other, only lacunes present at autopsy with
clinical history of "stroke."

were cortical strokes. Other leading causes of death
were cancer (20%), infection (17%), and gastrointestinal disease (8%).
Correlation of clinical symptoms and signs with
pathologic findings in these 167 patients with 324
lacunes revealed that 35 ischemic events occurred
in the 32 patients (19%) in Group A, 11 events
occurred in the 11 patients (7%) in Group B, 27
events occurred in the 26 patients (16%) in Group
C, and 11 events occurred in the 11 patients (7%) in
Group D. The remaining 87 patients (52%) were in
Group E. Thus, at least 19% of the patients with
lacunes were symptomatic (Group A), and as many
as 41% may have been symptomatic due to lacunar
infarcts (Groups A plus C plus D). Analyzed on the
basis of the number of lacunes, at least 11% were
symptomatic (Group A), and as many as 23% may
have been symptomatic (Groups A plus C plus D).
Similar analysis of a subset of patients with only
a single lacune at autopsy revealed that a range of
15-26% of such patients may have been symptomatic from their lacunes.
Among the 32 Group A patients with 35 ischemic
events attributable solely to lacunes (Table 4), pure
motor hemiparesis was the most common clinical
presentation (31%) and was followed in frequency
by aphasia plus right hemiparesis (20%), hemiparesis plus other symptoms (17%), and sensorimotor
dysfunction (11%); parkinsonism was infrequent
(3%), and pure sensory stroke was not seen. Since
patients examined by neurologists represent a more
reliable and detailed subset, the presenting signs of
23 lacunes in 21 such patients in Group A are
presented below in more depth (see also Table 4).
Eight Group A patients examined by neurologists
had pure motor hemiparesis. Lesions were found in

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Tuszynski et al Lacunar Stroke

1. Transverse sections of brainstem showing
(top) 0.7x1.0-cm cystic infarct of medial rostral basis
pontis (arrow) with (bottom) Wallerian degeneration of
ipsilateral medullary pyramid (arrow).
FIGURE

the posterior limb of the internal capsule in five and
in the basis pontis in two (Figure 1). The eighth
patient, with weakness restricted to the face and
arm, had a single 2x3x4-mm lacune in the left
caudate nucleus and anterior limb of the internal
capsule.
Five Group A patients examined by neurologists
had aphasia plus right hemiparesis. One had an
ischemic infarction of the left thalamus (Figure 2),
two had lesions of the left anterior internal capsule
and caudate or putamen, one had a left anterior
capsular lesion as well as a noncontiguous left
thalamic lesion, and the fifth patient had a small left
caudate lacune and "small infarcts of both basal
ganglia." Three of the five lacunes in these five
patients were >1 cm in size. Two of these five
patients had subsequent brainstem lacunes, associated with left hemiparesis and mutism in one (Figure
3) and with left sensorimotor dysfunction and dysarthria in the other (see below). Clinical and pathologic findings in these five patients with hemiparesis
and aphasia are summarized in Appendix 1.
Four Group A patients examined by neurologists
presented with mixed sensorimotor deficits, one of

993

whom also had dysarthria and a previous episode of
right hemiparesis and aphasia (see above). One
patient had a 1.7-cm cystic infarct of the right
posterior limb of the internal capsule, with extension to the adjacent thalamus and putamen (Figure
4), one had multiple 2-mm lesions bilaterally in the
basal ganglia and internal capsules; one had only a
lesion in the right putamen; and the fourth (with
dysarthria) had multiple 1-mm cystic pontine lesions.
Two Group A patients examined by neurologists
presented with left hemiparesis plus dysarthria.
One had a 0.5x0.5x1.5-cm lesion in the anterior
limb of the right internal capsule and the other had
a 1-cm lesion of the right basis pontis. No cortical
infarcts were seen. Two other Group A patients,
aged 77 and 89 years, presented with left hemiplegia
plus altered level of consciousness. Both were
hypotensive on admission, and one was septic; the
causes of death were sepsis and acute myocardial
infarction, respectively. Although the initial clinical
diagnosis at the time of admission in both patients
was vertebrobasilar insufficiency, autopsy revealed
several 2-3-mm infarcts in the right thalamus,
internal capsule, and left basal ganglia in one patient
and a single subacute 3-mm infarct in the right
posterior limb of the internal capsule in the other
patient. Basilar artery thrombosis or severe stenosis was not present.
Lastly, an 83-year-old man presented with a
5-year history of tremor, rigidity, and a shortstepped, shuffling, unsteady gait. Examination
revealed increased tone, cogwheeling, hyperreflexia, and bilateral extensor plantar responses.
Two neurologists diagnosed "extrapyramidal
disease." The patient died at home of appendicitis.
Autopsy showed a 2-mm cystic infarct of the left
lateral thalamus and multiple bilateral microscopic
infarcts of the globus pallidus and pons. Marked
vascular changes of lipohyalinosis were noted, but
neither hydrocephalus nor pathologic changes of
Parkinson's disease were present.
Additional Group A patients not examined by
neurologists were said to have had basilar insufficiency, right hemiparesis plus other deficits, a
"left MCA stroke," a "right CVA," a "left CVA,"
and a "stroke." However, only lacunes were
present at autopsy.
Discussion
The limitations of a retrospective study must not
be ignored. Its reliability depends upon the nonstandardized examining and charting skills of a
number of physicians and upon the thoroughness of
pathologic data that is largely unavailable for reexamination. Thus, the frequency of symptomatic
lacunes in our study may be underrepresented due
to incomplete reporting of symptoms by patients or
physicians and because many lacunes are smaller
than 1-cm sections used to study these brains anatomically. Similarly, the interpretation of information obtained from symptomatic patients depends

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994

Stroke Vol 20, No 8, August 1989

FIGURE 2. Coronal section
showing 1-cm cystic lacune
(arrow) in left thalamus with
ipsilateral hydrocephalus ex
vacuo.

upon the assiduousness of the examining physician,
the ability of the patient to cooperate in providing a
history, and the accuracy of the pathologic data. It
is hoped that the large size of our study and our
analysis of more detailed subsets of patients in
certain instances help to minimize the effects of
these potential sources of error. Clear patterns have
emerged from our review that merit presentation.
Confident verification must await the presentation
of correlative prospective data, however.
Lacunar infarctions were common, occurring in
6% of the 2,859 autopsies in our series and in 11% 10
and 10%13 of the autopsies in Fisher's series. In our
study, 91% of the lesions for which size was specified were <1 cm in size. They were usually multiple (average 1.9 per patient) and were most commonly located in the basal ganglia and less often in
the internal capsule, pons, and thalamus, a distribution paralleling that described by Fisher.10
Coexistent but noncontiguous cortical infarctions
were present in 49% of the symptomatic patients in
our series compared with 26% observed by Fisher.10
The high concurrence rate for cortical and subcortical infarction suggests shared risk factors and
possibly shared pathogenesis.
Hypertension is the most common risk factor for
lacunar infarcts. It was found in 64% of our patients
for whom clinical data were available, a figure that
correlates well with the range (57-75%) in published
series.1-7-9 The high incidence of 94% reported by
Fisher10 probably results from the fact that he used
a threshold for hypertension of > 140/90 mm Hg
whereas others have generally used a threshold of
160/95 mm Hg. Hypertension was also the most
common risk factor in our subset of 56 patients with
more detailed pathologic examination; hyperten-

sion occurred in 59% of these patients. However, it
was the sole risk factor in only 12.5%, although the
association of hypertension plus atherosclerosis was
frequent (46%). The incidence of normal intracerebral vessels or vessels showing mild to moderate
hyalinization among hypertensive patients was similar to that found in normotensive patients with
ASCVD. Severe pathologic changes, although infre-

FlGURE 3. Transverse section of rostral pons showing
0.3x.l.2-cm cystic infarct (arrow) in right basis pontis.
Centimeter scale. (Same patient as in Figure 2.)

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Tuszynski et al Lacunar Stroke

995

FIGURE 4. Coronal section
showing l.Oxl.S-cm
cystic
infarct (arrow) involving superior aspect of right internal
capsule, posterior putamen,
and small area of thalamus.
Remaining posterior limb of
ipsilateral internal capsule is
shrunken.

quent (14%), were confined to hypertensive patients
and were histologically similar to those changes
previously described by Fisher.3
Atherosclerosis is an important cause of lacunar
infarcts. The established association of ASCVD
with transient ischemic attacks14-16 and stroke17 can
be extended to lacunes. Risk factors associated
with atherosclerosis were common among our
patients. Diabetes was present in 34%, a figure
comparable to previous reports of 27%,18 29%,x and
11%.10 A family history of stroke was seen in only
17% of our patients, but 35% had a family history of
myocardial infarction. During life, coronary artery
disease was diagnosed in 47% of all patients in our
series, and at autopsy myocardial infarcts were
found in 52%. Forty-six percent of the patients were
smokers, a factor of uncertain significance with
regard to the risk of cerebrovascular disease.19-24
Among the subset of 56 patients with more detailed
pathologic data, ASCVD was the sole apparent
etiology of the lacunes in 30%. These patients were
normotensive and had systemic atherosclerosis with
normal or mild to moderate vascular changes in the
intraparenchymal brain vessels. Since none of the
autopsy reports described occlusive atherosclerotic
plaques in the appropriate penetrating arteries of
the circle of Willis and since the intraparenchymal
changes in the blood vessels were not severe, the
data suggest that atherosclerosis may give rise to
lacunes primarily via emboli from plaques in the
ascending aorta or major vessels in the neck, including the carotid bifurcation, which were not examined. Indeed, slightly more than half of the normotensive atherosclerotic patients had clear sources
of emboli as described in the postmortem records.
Embolism from the heart valves was the sole etiol-

ogy of the lacunes in 10.7% of the patients and was
due to rheumatic heart disease in three and to
probable nonbacterial thrombotic endocarditis in
three. None of these six patients had either hypertension or ASCVD. While the carotid bifurcation
was not studied in these six patients and thus
cannot be definitively excluded as a source of
embolism, isolated atherosclerosis in the neck is
rare in the absence of systemic atherosclerosis at
autopsy.
The incidence of asymptomatic patients with lacunar infarcts in our series was high (59-81%).
Although this incidence is higher than in previous
studies, which have estimated the incidence as
roughly 30-33%,8>9 those studies may have underestimated the frequency of asymptomatic infarcts
since only symptomatic patients were studied and
since the authors employed computed tomography
(CT) rather than autopsy to detect lesions. Fisher
has suggested that "the first or only lacune tends to
be symptomatic."2 However, only 15-26% of our
patients with one lacune were symptomatic. This
finding indicates that the first or only lacune is not
necessarily symptomatic and that patients are more
likely to be symptomatic if more than one lacune is
present.
Forty-four percent of our patients were symptomatic from all causes of cerebrovascular disease,
including cortical strokes. Fisher noted an incidence of 23%,10 supporting our conclusion that
most lacunes are asymptomatic.
The distribution of symptoms and signs of lacunes
in our series of patients differs from that in previous
reports. Aphasia and mixed sensorimotor deficits
were relatively frequent, and pure sensory stroke
was not reported. In agreement with other reports,

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996

Stroke Vol 20, No 8, August 1989

pure motor hemiparesis was the most common
presenting symptom, occurring in 31% of the patients
compared with reports of 21-60% in the literature.8-25
Most lesions causing pure motor hemiparesis were
located in the posterior limb of the internal capsule
or basis pontis, corresponding to previous
descriptions.3'26-27
Aphasia plus right hemiparesis was the second
most common presentation, occurring in 20% of our
patients. Language deficits were either mixed or
predominantly expressive, with sparing of repetition in some cases, and all lesions were left-sided
and involved either the thalamus, anterior internal
capsule, or basal ganglia. Subcortical aphasia has
been well documented by CT studies and by occasional clinicopathologic case reports,2'28-40 but a
frequency as high as 20% has not previously been
documented in patients with lacunes. Aphasia with
variable expressive and receptive components associated with lesions in the dominant anterior limb of
the internal capsule, the head of the caudate, and
the putamen has been described in at least six
patients by CT scan,29 and mild fluent aphasia
associated with lesions in the posterior limb of the
dominant internal capsule was reported in six
patients by CT scan.28-32 Single case reports have
documented right hemiparesis plus expressive aphasia with an infarct in the anterior limb and genu of
the internal capsule and adjacent inferior corona
radiatum2 and right hemiparesis plus anomia and
word-finding difficulty with a dominant posterior
capsular infarct.34 Mutism has also been reported
following bilateral capsular lesions.2 Aphasia resulting from lesions of the basal ganglia33-35 or
thalamus36-40 has been described in CT-based studies without pathologic confirmation and in three
clinicopathologic reports.41-43
Several of these reports are subject to doubts
regarding the strictly subcortical localization of
their lesions, due either to a lack of pathologic
confirmation or to the presence of symptoms in
addition to aphasia, including altered sensorium and
eye movement abnormalities. Nonetheless, taken
together the available evidence supports the concept of strictly subcortical aphasia.
Factors that might account for a failure to recognize subcortical aphasia more commonly in the past
include: 1) a failure to consider subcortical localization of a language deficit; 2) the prolonged survival
of patients with subcortical lesions, making opportunities for clinicopathologic correlations rare; and
3) the unavailability, until recently, of the technology with which to visually localize lesions during
life. Of note, most reports of subcortical aphasia
have appeared since the availability of highresolution CT scanning. Furthermore, our study is
only the second large series of patients with pathologically verified subcortical infarcts, so there is no
clear precedent suggesting that subcortical aphasia
is rare. Thus, aphasia should not preclude the
diagnosis of lacunar infarction. Although overlap

with cortical syndromes exists, subcortical localization of hemiparesis and aphasia may be suggested if
accompanying sensory deficit, neglect, left-right
confusion, and other manifestations of cortical dysfunction are not present and if aphasia is transcortical in nature.
Sensorimotor dysfunction was another common
presentation of lacunar infarction in our series,
affecting 11% of the patients. Lesions were found in
the posterior limb of the internal capsule in three
patients and in the base and lateral portion of the
pons in a fourth. At least 15 cases of sensorimotor
dysfunction from lacunar infarction are described in
the literature.7'9'25-44-47 Mohr et al44 described a
pathologically confirmed case caused by a single
4x4x2-mm thalamocapsular lacune. Subcortical infarcts can interrupt projecting thalamocortical sensory fibers48 as well as motor fibers, without involving thalamic nuclei, to produce sensorimotor
deficits.7'9 Small capsular hemorrhages have also
resulted in sensorimotor loss.49 In addition, reports
of "pure" motor hemiparesis often include subjective sensory complaints.26 Others have reported
that sensorimotor dysfunction occurs in 1%,9 17%,8
33%,7 and 38%50 of symptomatic lacunes. Our cases
support the assertion that sensorimotor dysfunction
may be a common presentation of lacunar infarction. As with hemiparesis plus aphasia, the absence
of other cortical signs should lead to suspicion of a
subcortical lesion.
Two patients presented with left hemiparesis plus
dysarthria. One had a lesion of the anterior limb of
the nondominant internal capsule, and the other had
lesions in the right basis pontis, right thalamus, and
right basal ganglia. Hemiparesis plus dysarthria has
been described with lesions of the anterior limb of
the nondominant internal capsule,29 and Fisher26
noted slurred speech in two thirds of patients with
"pure" motor hemiplegia. Thus, lesions of the
dominant internal capsule can produce aphasia plus
hemiparesis, whereas lesions of the nondominant
internal capsule can produce dysarthria plus
hemiparesis.29
Lacunes can occur with altered levels of consciousness. Two elderly patients in our series had
left hemiplegia plus altered mentation with a single
infarction in the right internal capsule and with
bilateral lacunes, respectively. Both also had concurrent systemic compromise (myocardial infarction, sepsis, and relative hypotension) that presumably accounted for their diminished alertness. Fisher2
presented a case of "pure motor hemiparesis with
confusion" reportedly caused by a 1.2-cm lacune in
the anterior limb and anterior part of the posterior
limb of the right internal capsule, presumably interrupting thalamofrontal connections. Lacunes can
therefore directly or indirectly alter the level of
consciousness, although coma has not been reported
with lacunes.
Finally, one patient presented with progressive
rigidity, tremor, and short-stepped, shuffling,

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Tuszynski et al Lacunar Stroke
unsteady gait, the "lacunar state" of Marie.51 Marie
attributed this progressive decline to the cumulative
effect of multiple lacunes. Given the relatively small
number of lacunes and the presence of ventricular
dilatation in many similar cases in the literature,
Fisher2 attributed the lacunar state to occult normal
pressure hydrocephalus. The absence of ventricular
dilatation at autopsy in our present case tends to
support the first view.
Pure sensory stroke was not described in the
patients in our series. Fisher2 stated that pure
sensory stroke is the most common lacunar presentation, whereas Donnan et al9 and Pullicino et al8
had no pure sensory lacunar strokes in their series
and Weisberg7 noted pure sensory strokes in approximately 8% of the presentations. Similarly, patients
with ataxic hemiparesis plus clumsy-hand dysarthria were not present among Group A patients,
although possible examples of these presentations
occurred in Group C patients. In agreement with
previous accounts,2-4 lacunar infarcts with visual
field cuts or apraxias were not encountered.
Although our series suggests a different clinical
spectrum from previous series of patients with
lacunes, important clinical distinctions still distinguish lacunar from cortical infarcts. Visual field
defects, neglect,52-53 agnosias, apraxias, acalculias,54
behavioral abnormalities, auditory deficits, and seizures are very rare with lacunes that spare the
thalamus. In contrast, pure motor hemiparesis, the
most common clinical finding with lacunes, occurs
rarely with cortical stroke.55-58 Lacunar strokes
that are more difficult to distinguish from cortical
infarcts (e.g., aphasic/hemiparetic presentations)
may be suspected when deficits are confined to one
or two modalities (e.g., motor and language) rather
than to several modalities. Thus, the entity of
lacunar infarction, albeit more heterogeneous pathogenetically, epidemiologically, and clinically than
previously believed, remains. Attempts at recognition are important since lacunar strokes usually
have a favorable prognosis.2-6-50
Appendix 1: Case Reports of Aphasic Patients
A 77-year-old hypertensive, diabetic, righthanded man presented with the abrupt onset of a
moderately severe right hemiparesis and aphasia.
Language testing showed mild comprehension
impairment, anomia, diminished fluency, occasional paraphasic errors, intermittent verbal preservation, and intact repetition. The deficits gradually
improved, but he was readmitted with the abrupt
onset of left hemiplegia and mutism 38 days later.
Minimal improvement occurred, and he died 71
days later of pneumonia. Autopsy revealed a 1x2cm cystic infarct in the left lateral thalamus, extending to the adjacent posterior limb of the internal
capsule (Figure 2), and a second 0.3xl.2-cm cystic
infarct in the right basis pontis (Figure 3). No
cortical lesions were present.

997

A 66-year-old hypertensive, diabetic, righthanded woman developed left hemiparesis and dysarthria that improved over several days. One year
later, right hemiparesis and dysarthria occurred
with a gradual onset and progressed over the next
12 hours to right hemiplegia and expressive language dysfunction characterized by frequent paraphasic errors, diminished fluency, and normal comprehension. The patient regained fluency the next
day but remained dysarthric and hemiplegic on the
right. The patient died 1 month later of pneumonia
and sepsis. Autopsy revealed a 1-cm cystic infarct
of the anterior limb of the left internal capsule and
caudate nucleus, a 1-cm cystic infarct of the ventral
half of the right basis pontis, and several 2-mm
cystic infarcts in the right thalamus and basal ganglia. No cortical infarcts were present.
A 78-year-old hypertensive right-handed woman
presented with the abrupt onset of right hemiparesis
and dysphasia characterized by paraphasic errors.
She improved little and died 2 years later of aspiration pneumonia. Autopsy revealed multiple small
cystic infarcts bilaterally in the anterior internal
capsules, putamina, and thalami. No other lesions
were present grossly or microscopically.
A normotensive 57-year-old right-handed woman
in chronic atrial fibrillation suffered the abrupt onset
of right hemiparesis and expressive language difficulties that resolved over 6 months. Seven years
later she developed left-sided weakness and dysarthria, then became septic and died. Autopsy revealed
three infarctions: a 1-cm cystic lesion in the left
putamen and globus pallidus with extension into the
anterior internal capsule, a subacute embolic 2x2cm right lateral occipital infarction, and a subacute
embolic lxl-cm right frontal infarction.
Lastly, a 52-year-old right-handed man with a
long-standing history of poorly controlled hypertension and previous myocardial infarction presented
with a right thalamic hemorrhage. Initial stupor and
left hemiparesis improved over several months to a
mild residual left hemiparesis. Two years later he
noted recurrent episodes of right-sided numbness and
expressive language difficulty lasting minutes, culminating 1 week later in the progression over 13 hours of
right hemiplegia, right hemisensory deficit to pin-prick
only, and language difficulties. Comprehension and
naming were intact, but word-finding difficulty was
present. One week later the deficits had improved
considerably, and 2Vi weeks after admission function
had returned to baseline. He died of myocardial
infarction 5 years later. Autopsy revealed a 2x7-mm
cystic infarction of the left caudate nucleus, several
additional 1-2-mm cystic infarctions in both basal
ganglia, and an old l.lxl.5-cm previously hemorrhagic lesion of the right thalamus and caudate nucleus.
No cortical infarctions were present.
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KEY WORDS • lacunar infarction • risk factors • pathology

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Risk factors and clinical manifestations of pathologically verified lacunar infarctions.
M H Tuszynski, C K Petito and D E Levy
Stroke. 1989;20:990-999
doi: 10.1161/01.STR.20.8.990
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1989 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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