Lacunar infarcts

Author:
Jamary Oliveira Filho, MD, MS, PhD
Section Editor:
Scott E Kasner, MD
Deputy Editor:
John F Dashe, MD, PhD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Mar 2020. | This topic last updated: Dec 04, 2018.

INTRODUCTIONLacunar infarcts are small (0.2 to 15 mm in diameter) noncortical

infarcts caused by occlusion of a single penetrating branch of a large cerebral artery
[1]. These branches arise at acute angles from the large arteries of the circle of Willis,
stem of the middle cerebral artery (MCA), or the basilar artery. Although this
definition implies that pathological confirmation is necessary, diagnosis in vivo may
be made in the setting of appropriate clinical syndromes and radiological tests.

HISTORYDechambre first used the term "lacune" in 1838 to describe softenings in

subcortical regions of the brain found on autopsy [2]. At the time, there was dispute
regarding whether these lacunes were caused by encephalitis, a late phase of a small
hemorrhage, or ischemic necrosis. Marie in 1901 first described a clinical syndrome
associated with multiple lacunes, characterized by sudden hemiplegia with good
recovery, a characteristic gait with small steps ("marche a petits pas de Dejerine"),
pseudobulbar palsy, and dementia [3].

In the 1960s, careful clinicopathological correlations by Fisher generated the so-called

"lacunar hypothesis," which suggested that lacunes are due to a chronic vasculopathy
related to systemic hypertension, cause a variety of defined clinical syndromes, and
imply a generally good prognosis [4].

The introduction of CT and MRI has generated data that both supports and opposes
the lacunar theory [5,6]. Some authors have suggested abandoning the concept
altogether [7,8]. Detractors of the lacunar hypothesis note the lack of animal data or
an animal model of lacunar infarction and the demonstration of embolic sources from
the heart, aorta, or large arteries in a substantial percentage of lacunar strokes [9,10].
Proponents concede that some small number of lacunes may result from emboli, but
they point out that the proportion of embolic sources found in association with lacunar
syndromes is far lower than for other ischemic stroke types and that there are clear
clinical and epidemiologic reasons to separate lacunes from other ischemic stroke
subtypes [10,11].

One of the major difficulties in interpreting these data stems from the inability of
imaging techniques to show that an infarct was due to occlusion of a single
penetrating artery. Furthermore, various studies have used different sets of criteria to
define "lacunar infarcts" and the many lacunar syndromes [12,13]. However,
continuing publications on the subject have demonstrated that the term "lacune" is
clinically useful and has gained wide acceptance in the literature.

VASCULAR ANATOMYMost lacunes occur in the basal ganglia (putamen, globus

pallidus, thalamus, caudate), subcortical white matter (internal capsule and corona
radiata), and pons [4,14,15]. These locations correspond to vascular territories of the
lenticulostriate branches from the anterior and middle cerebral arteries, the recurrent
artery of Heubner from the anterior cerebral artery, the anterior choroidal artery from
the distal internal carotid artery, thalamoperforant branches from the posterior
cerebral artery, and paramedian branches from the basilar artery (figure 1) [16,17].
These small branches originate directly from large arteries, making them particularly
vulnerable to the effects of hypertension, probably explaining this peculiar
distribution.

A study using fluorescent and radiopaque dye injection techniques has demonstrated
that penetrating vessels supply distinct microvascular territories of the basal ganglia,
with minimal overlap and sparse anastomoses between the penetrating vessels [17].
The ultimately terminal rather than anastomotic nature of these vessels is another
factor explaining the predisposition of this region to lacunar infarction.

ETIOLOGYSeveral mechanisms for small vessel disease and lacunar infarction have
been described [1,18-20]:

●Lipohyalinosis of the penetrating arteries is considered the usual cause, particularly

of smaller infarcts (3 to 7 mm in length).

●Microatheroma of the origin of the penetrating arteries coming off the middle
cerebral artery stem, circle of Willis, or distal basilar or vertebral arteries. This
mechanism has been proven pathologically by serial section for the basilar artery.

●In some cases, not proven pathologically, tiny emboli have been suspected as the
cause of these small infarcts.

●Failure of the cerebral arteriolar and capillary endothelium (ie, endothelial

dysfunction) and disruption of the associated blood-brain barrier.  

The first two mechanisms are proven pathologically [1], and generally regarded as a
consequence of systemic hypertension. In a retrospective study, lacunar infarcts in the
territory of a single perforating branch artery of the middle cerebral artery (MCA)
were found significantly more often in association with atherosclerotic MCA
occlusive disease than with internal carotid occlusive disease or cardiac embolism
[21]. This observation supports the hypothesis that some lacunar strokes are caused by
parent artery (eg, MCA or basilar artery) atheroma that occludes the origin of the
penetrating artery.

The third mechanism (embolism) is supported both experimentally [22] and by case
reports of lacunes in patients with high-risk cardiac sources for emboli [23] or
following cardiac and arch angiography [24].
Other mechanisms have been proposed to account for lacunar infarcts, but none are
pathologically proven. One alternate explanation is that failure of the arteriolar and
capillary endothelium and the blood-brain barrier leads to small vessel disease,
lacunar stroke, and white matter lesions [19,25-28]. This failure allows extravasation
of blood components into the vessel wall, which results in perivascular edema and
damage to the vessel wall, perivascular neurons, and glia [29,30]. However, one
neuropathologic study found no compelling evidence of a specific cerebral endothelial
response in patients with small vessel disease [31].

The pathology of lacunar infarcts may be changing as the medical management of

hypertension becomes more effective [32]. A decline in the number of lacunes per
patient in comparable pathology series has been attributed to the introduction of
antihypertensive therapy [1]. Another neuropathology study in lacunar infarcts found
only 69 percent of patients with evidence of systemic hypertension and rare cases of
classic lipohyalinosis [32], further suggesting that modern antihypertensive therapy
may have changed the natural history and/or pathophysiology of lacunes.

Of interest regarding mechanism, a systematic review of 19 cohort studies involving

5864 patients with ischemic stroke found that those who had a lacunar infarct as the
index event were more likely to have lacunar than nonlacunar stroke recurrence,
lending some support to the notion that lacunar strokes represent a different form of
arteriopathy than other ischemic stroke subtypes [33].

Studies investigating possible stroke mechanisms in lacunar infarcts have found

carotid stenosis in 13 to 23 percent [34,35] and cardiac sources in 18 to 24 percent
[35,36] of patients with a radiologically-demonstrated lacunes. These rates are much
lower than those of patients with cortical infarcts [34,37] and may be similar to
asymptomatic elderly populations, making the argument of a causal relationship
between the verified sources and the lacunes difficult to prove. It also appears that
patients with lacunar infarcts more often have milder degrees of carotid stenosis than
those with cortical infarcts [38]. On the other hand, ipsilateral carotid stenosis appears
to be more common than contralateral stenosis, which supports a possible causal
relationship [39].

In some reports, multiple acute to subacute subcortical or small cortical infarcts have
been detected by diffusion-weighted magnetic resonance imaging (DWI), suggesting
an embolic source.

●One study using DWI in patients presenting with a lacunar syndrome found that 16
percent had multiple infarcts detected as DWI-hyperintense lesions, implying that all
lesions were acute to subacute (image 1) [40]. This subgroup more frequently
harbored a proximal embolic source than patients with single lesions (p <0.05).

●Another case series evaluated 73 patients presenting with lacunar syndromes; all
underwent DWI as well as extensive neurovascular and cardiac evaluations for
potential embolic sources [41]. DWI radiologic patterns suggestive of nonlacunar
infarction (mainly embolism) were seen in a total of 30 patients (41 percent); of these,
16 had one large or multiple acute lesions within a single vascular territory, and
another 14 had multiple infarcts in different vascular territories [41]. Patients with
more than one infarct on DWI were significantly more likely to have a clinically
proven embolic source, although no embolic source was found in nine patients with a
DWI pattern suggestive of a nonlacunar/embolic stroke mechanism.

EPIDEMIOLOGYThe incidence rate of lacunar infarcts depends upon the population

studied:

●In a population-based study from Italy, the incidence rate of lacunar infarct
standardized to the 1996 European population was 26.3 per 100,000 population [42].
Lacunes accounted for 15 percent of first-ever ischemic strokes.

●Among a community-based population of predominantly white residents of

Rochester, Minnesota, the incidence rate of lacunar infarct between 1985 and 1989
was 29 per 100,000 population [43]. Lacunes accounted for 16 percent of first-ever
ischemic strokes.

●Among a community-based population of black residents of a metropolitan area of

Cincinnati, Ohio, the incidence rate of lacunar infarct was 52 per 100,000 population
[44]. Lacunes accounted for 22 percent of first-ever ischemic strokes.

●Among populations of patients in referral based studies, lacunes account for a larger
proportion of ischemic strokes, 26 percent in the Stroke Data Bank [34].

One group estimated that 18 percent of first ischemic strokes in the United States are
lacunes [43]. This compares with 16 percent due to large vessel atherosclerosis with
stenosis, 26 percent cardioembolic, 3 percent due to an uncommon mechanism, and
37 percent of unknown or no obvious cause.

A population-based study from Japan suggests that the incidence of lacunar stroke has
been steadily declining since the 1960s [45]. This finding was attributed to improved
control of hypertension and decreased prevalence of smoking during the last 40 years.

RISK FACTORS AND ASSOCIATIONSAs mentioned above, two of the three

described mechanisms for lacunar stroke are related to a chronic vasculopathy
associated with systemic hypertension. (See 'Etiology' above.)

Other likely risk factors for lacunar infarction include diabetes mellitus and possibly
smoking, age, and low-density lipoprotein (LDL) cholesterol [46].
Hyperhomocysteinemia has been associated with an increased risk of ischemic stroke
and lacunar infarction in several studies [47-49]. (See "Overview of homocysteine".)

Hypertension and diabetes — Hypertension and diabetes mellitus are associated with

an increased risk of stroke in general. Whether they are more commonly associated
with lacunar stroke and small vessel disease compared with other stroke subtypes (as
many believe) is not clear, since the evidence is conflicting [43,50-54]. The answer
may depend upon the population studied and the criteria used to define lacunar-type
infarction.

One explanation for the difference in lacunar stroke incidence rates between whites
and blacks cited above (see 'Epidemiology' above) is a higher incidence of risk factors
such as diabetes and hypertension among blacks [44]. In the community-based study
of blacks in Cincinnati, Ohio, the odds ratios of first-ever lacunar infarct among
patients with diabetes or hypertension were 4.4 and 5.0, respectively, compared with
nondiabetic and normotensive individuals [44]. The attributable risk (proportion of
cases that can be attributed to the risk factor) for these two diseases were 30 and 68
percent, respectively (hypertension has a greater impact than diabetes because of its
higher overall prevalence in the population). The rates of hypertension and current
smoking were found to be significantly increased in patients with lacunar infarcts
compared with other stroke subtypes.

Other studies have also found a difference in the incidence of risk factors between
patients with lacunar stroke and those with other stroke subtypes. In the Stroke Data
Bank, patients with lacunar stroke had fewer previous transient ischemic attacks
(TIAs) and strokes than those with large vessel atherosclerotic infarction and,
compared with patients who had cardioembolic strokes, those with lacunar infarcts
more frequently had hypertension and diabetes [34].

These findings contrast with some other community-based studies [43,53]. As an

example, in the Oxfordshire Community Stroke Project, a study of first-ever stroke,
comparison between the risk factor profiles of patients with lacunar infarction and
carotid artery distribution infarct involving the cortex found that the two groups did
not differ in the prevalence of prestroke hypertension or markers of sustained
hypertension, or in the prevalence of other risk factors for ischemic stroke such as
diabetes mellitus, previous TIA, cervical bruit, peripheral vascular disease, or
cigarette smoking [53]. Similarly, the Rochester, Minnesota study found no greater
incidence of diabetes and hypertension among patients with lacunar infarcts and those
with other stroke subtypes [43].

Genetic factors — The APOE e4 allele may confer some risk of developing small
vessel pathology, as there is evidence that APOE e4 carriers are at increased risk for
the development of subcortical white matter lesions [55]. Additional genetic factors
that may play a role in the development of small vessel disease and lacunar stroke
include the MTHFR C677T genotype [56] and the angiotensin converting enzyme
(ACE) insertion/deletion polymorphism [57]. These observations require further
confirmation.

Finally, several rare conditions are characterized by hereditary cerebral small vessel
arteriopathy:

●Cerebral autosomal dominant arteriopathy with subcortical infarcts and

leukoencephalopathy (CADASIL). (See "Cerebral autosomal dominant arteriopathy
with subcortical infarcts and leukoencephalopathy (CADASIL)".)

●Familial cerebral amyloid angiopathy, an important cause of primary lobar

intracerebral hemorrhage in the elderly, characterized by the deposition of
congophilic material in small to medium-sized blood vessels of the brain and
leptomeninges. (See "Cerebral amyloid angiopathy".)

●Autosomal dominant retinal vasculopathy with cerebral leukoencephalopathy and

systemic manifestations, which is associated with mutations in the TREX1 gene [58-
63]. This disorder is known also by a variety of other names, including retinal
vasculopathy with cerebral leukodystrophy (RVCL), cerebroretinal vasculopathy,
hereditary vascular retinopathy, and hereditary endotheliopathy with retinopathy
nephropathy and stroke (HERNS). Manifestations include visual impairment and
neurologic involvement with focal deficits, migraine, cognitive impairment,
psychiatric disturbances, and seizures [63]. The neurologic involvement is related to
progressive cerebral white matter lesions. Common systemic manifestations include
liver disease, nephropathy, anemia, hypertension, Raynaud phenomenon, and
gastrointestinal bleeding.

●Cerebral autosomal recessive arteriopathy with subcortical infarcts and

leukoencephalopathy (CARASIL) due to HTRA1 gene mutations [64,65].

●Cathepsin A–related arteriopathy with strokes and leukoencephalopathy

(CARASAL), an autosomal dominant, adult-onset disorder caused by a mutation in
the CTSA gene [66].

●Autosomal dominant small vessel disease caused by heterozygous HTRA1 gene

mutations [67].

●Brain small vessel disease with hemorrhage [68-71].

While all of these conditions affect small vessels and may theoretically manifest as a
classic lacunar syndrome, CADASIL is most likely to do so. (See "Cerebral
autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL)", section on 'Ischemic stroke and transient ischemic attacks'.)

CLINICAL FEATURESAcute identification of lacunar syndromes is important in

triaging medical resources, choosing among treatment modalities, and predicting
clinical outcome. As a general rule, lacunar syndromes lack findings such as aphasia,
agnosia, neglect, apraxia, or hemianopsia (so-called "cortical" signs). Monoplegia,
stupor, coma, loss of consciousness, and seizures also are typically absent.

Penetrating artery occlusions usually cause symptoms that develop over a short period
of time, typically minutes to hours (figure 2). However, a stuttering course may ensue,
as with large artery thrombosis, and symptoms sometimes evolve over several days.
In fact, lacunar infarction is the main ischemic stroke subtype associated with
worsening motor deficits after hospital admission [72].

More than 20 lacunar syndromes have been described. Five have been validated as
being highly predictive for the presence of lacunes radiologically:

●Pure motor hemiparesis

●Pure sensory stroke

●Ataxic hemiparesis

●Sensorimotor stroke

●Dysarthria-clumsy hand syndrome

As a group, the presence of these syndromes has a positive predictive value of 87 to
90 percent for detecting a radiological lacune [73,74], although some clinical
syndromes are more predictive than others [75-79]. Preceding TIAs and nonsudden
onset may increase the positive predictive value for these lacunar syndromes [80].
Predicted infarct locations in relation to clinical manifestations are shown in the Table
(table 1).

Syndrome recognition may be more difficult in the hyperacute setting. A study of

patients admitted within 6 hours of symptom onset reported only a 30 percent positive
predictive value [81].

Other syndromes that have not been studied in large clinical series but that may be
related to lacunar infarcts are shown in the Table (table 2). The syndrome of multiple
subcortical infarcts will be discussed in addition to the five syndromes mentioned
above since interest has arisen regarding whether this entity can cause dementia.

Pure motor hemiparesis — Pure motor hemiparesis is the most frequent syndrome in

most clinical series, accounting for 45 to 57 percent of all lacunar syndromes
[34,73,82-84]. It is characterized by weakness involving the face, arm, and leg on one
side of the body in the absence of "cortical" signs (aphasia, agnosia, neglect, apraxia,
or hemianopsia) or sensory deficit.

The motor deficit may develop as a single event or, less frequently, be preceded by
hemiplegic TIAs [1]. A series of the latter cases has been described as the "capsular
warning syndrome," which was found to be predictive of an acute internal capsule
infarct on head CT [85]. Some of these cases may arise due to penetrating branch
ischemia from a diseased "parent" vessel (MCA stem or basilar) causing intermittent
and fluctuating symptoms.

Pure sensory stroke — Pure sensory stroke is defined as numbness of the face, arm,
and leg on one side of the body in the absence of motor deficit or "cortical" signs [86].
It is found in 7 to 18 percent of lacunar syndromes in case series [34,73,83,84], but its
prevalence is probably underestimated because many cases present as TIA and were
not included in the series.

Ataxic hemiparesis — Ataxic hemiparesis is responsible for 3 to 18 percent of lacunar

syndromes in case series [34,73,83,84,87]. Patients characteristically develop
ipsilateral weakness and limb ataxia that is out of proportion to the motor deficit.
Some patients may exhibit dysarthria, nystagmus, and gait deviation towards the
affected side. As with other lacunar syndromes, the above-mentioned "cortical" signs
are absent.

Sensorimotor stroke — Sensorimotor stroke is characterized by weakness and

numbness of the face, arm, and leg on one side of the body in the absence of the
aforementioned "cortical" signs [88]. It is responsible for 15 to 20 percent of lacunar
syndromes [34,73,83,84].

Sensorimotor strokes arise from infarcts involving the posterolateral thalamus and
posterior limb of the internal capsule. The exact vascular anatomy is debated.
Theoretically, penetrating arteries from the posterior cerebral artery (PCA) supply the
thalamus and the internal capsule is supplied from the lenticulostriate branches of the
MCA. Occlusion of a single penetrating artery involving both arterial territories is
difficult to implicate; the site of vascular occlusion was not identified in the original
case description [88].

Dysarthria-clumsy hand syndrome — Dysarthria-clumsy hand syndrome is the least

common of all lacunar syndromes in most case series, accounting for 2 to 6 percent of
lacunar syndromes [34,73,83,84,89]. Facial weakness, dysarthria, dysphagia, and
slight weakness and clumsiness of one hand are characteristic. There are no sensory
deficits or "cortical" signs.

Multiple subcortical infarcts and dementia — As previously mentioned, the first

description of a lacunar syndrome in 1901 included a chronic neurologic course with
episodes of mild hemiparesis progressing to abnormal gait, pseudobulbar signs,
dysarthria, incontinence, and dementia [3]. Cases such as these have become rare,
even in patients with multiple subcortical infarcts, and questions have been raised
about whether the patients in the original description had unrecognized normal-
pressure hydrocephalus [1].

The relationship between subcortical strokes and cognitive deficits has been explained
by interruption of neural connections with an indirect effect upon cortical metabolism
and perfusion, so-called "diaschisis." This hypothesis is supported by case series of
CT-demonstrated subcortical infarcts presenting with transcortical aphasia or neglect
[90,91], as well as by functional studies using SPECT or positron emission
tomography (PET) [92-94].

One study using PET compared cortical glucose metabolism in patients with dementia
and subcortical infarcts, patients with subcortical strokes and normal cognitive
function, and controls without cognitive impairment or stroke [94]. Global
metabolism was impaired proportionally to cognitive decline, while regional right-
sided frontal lobe metabolism was impaired in relationship to the presence of
subcortical infarcts. No relationship was found between the number or location of the
subcortical infarcts and the presence of cognitive impairment.

Some but not all longitudinal studies have found an association between the
development of new lacunes and cognitive decline [95-98]. As an example, a
prospective MRI study of 1015 patients without baseline dementia found that silent
subcortical infarcts were associated with later development of dementia over four
years of follow-up [95]. Patients developing dementia more often had thalamic
strokes at baseline and accumulated new subcortical lesions on a second MRI scan.

Taken together, these findings indicate a potential mechanism for dementia in

subcortical strokes and the need to develop more effective strategies to prevent the
accumulation of silent subcortical infarcts. (See "Etiology, clinical manifestations,
and diagnosis of vascular dementia".)

DIAGNOSISUnlike our ability to visualize large vessel occlusion by vascular

imaging (conventional angiography and CT or MR angiography), there is no clinically
available method to confirm the presence of a single penetrator artery occlusion.
Thus, the diagnosis of lacunar infarction in vivo relies upon finding a clinical
syndrome that is consistent with the location of a small noncortical infarct seen on CT
or MRI. Brain imaging with CT or MRI is also useful to exclude other potentially life-
threatening diagnoses such as intracerebral hemorrhage or subdural hematoma.
Investigation of the underlying stroke mechanism (eg, thrombosis versus embolism) is
still indicated to exclude potentially correctable causes of recurrence.

This section will primarily discuss the diagnostic tests used to confirm or exclude the
clinical suspicion of a lacune (eg, CT, MRI, DWI). The evaluation of stroke
mechanisms is discussed in more detail separately. (See "Overview of the evaluation
of stroke".)

Computed tomography — Noncontrast head CT is the initial imaging modality for

most patients presenting with an acute stroke syndrome. CT has low sensitivity for
detecting lacunes (30 to 44 percent) [14,99]. The sensitivity of CT for lacunes in the
hyperacute phase (<6 hours) has not been systematically studied, but is likely to be
even lower; thus, a lacune seen on CT in this time window is more frequently chronic
and not related to the clinical symptoms. CT also is limited in identifying posterior
fossa infarcts and in defining the degree of cortical extension in subcortical infarcts.

Magnetic resonance imaging — MRI has been extensively studied in lacunar infarcts.

It has a higher sensitivity and specificity than CT [99,100], and is better for defining
the exact anatomical localization. In one study, for example, MRI detected lacunar
infarcts in 19 of 22 patients with compatible symptoms, compared with 11 found by
CT [100]. A second report confirmed that MRI was superior to CT for detecting
lacunes; the sensitivity of MRI was greatest for patients who presented with pure
motor hemiparesis, detecting 85 percent of lesions [99]. MRI usually shows infarcts
within 8 hours of symptom onset.

An inherent difficulty of both CT and conventional MRI is the ability to differentiate

between acute and chronic lesions. In one study, 16 percent of patients presenting
with a lacunar syndrome had at least two lesions on conventional MRI that correlated
with clinical symptoms [14]. Furthermore, in patients presenting with a lacunar
syndrome, multiple chronic subcortical lesions are not rare, occurring in
approximately 42 to 75 percent of cases [4,99]. For these reasons, knowledge of
possible lesion locations based upon neurologic findings is necessary before
implicating a particular lesion found on MRI as responsible for the clinical symptoms
(table 1).

Diffusion-weighted imaging — Diffusion-weighted imaging (DWI) is a fast MRI

technique that demonstrates a hyperintense signal whenever there is an area of
restricted water diffusion, as occurs during acute ischemia. DWI has the advantages of
a higher sensitivity for acute lesions than T2-weighted MRI or FLAIR, ability to
differentiate between acute and chronic lacunar infarcts, and ability to identify
multiple acute infarcts potentially linked to embolic sources [40,101,102]. In one
study, 25 percent of DWI-hyperintense lacunar infarcts were either not seen or
mistakenly called "chronic" on T2 or FLAIR imaging [102]. This finding suggests
that patients require DWI to define the clinically appropriate infarct when multiple
subcortical infarcts of various ages are present. (See "Neuroimaging of acute ischemic
stroke", section on 'Magnetic resonance imaging'.)
The size of acute lacunar infarction is overestimated on DWI by approximately 40
percent when compared with final infarct size at 30 days or more after stroke onset on
conventional MRI (T2 or FLAIR sequences) and CT [103].

Other studies — For most situations, MRI with clinical correlation adequately defines
the infarct location and excludes a cortically-based infarct. The extent of the
remaining diagnostic investigation will depend upon the resources available and
patient characteristics.

Further testing is of low yield in patients suspected of having a lacunar infarction who
have the typical risk factors for penetrating artery disease (eg, hypertension or
diabetes mellitus), clinical neurologic findings suggestive of a typical lacunar
syndrome, and a corresponding radiologic lacunar infarct (table 1). On the other hand,
more extensive investigation of potential embolic sources may be necessary in young
patients with no cerebral risk factors and in patients with multiple lesions on DWI.

Vascular imaging (CTA or MRA) can be performed at the same time as brain imaging
(CT or MRI) to exclude occlusion of the parent feeding artery, a condition that can
mimic a lacunar infarct [1,18,104]. It is particularly important to perform intracranial
vascular imaging in blacks and persons of Asian descent, since intracranial large
artery occlusive disease is common in these populations. An alternative diagnostic test
to exclude intracranial occlusive disease is transcranial Doppler (TCD), a technique
that measures the blood flow velocities in the large intracranial arteries using an
ultrasound probe placed over the orbit, temporal bone, and foramen magnum. (See
"Neuroimaging of acute ischemic stroke", section on 'CT angiography (CTA)' and
"Neuroimaging of acute ischemic stroke", section on 'MR angiography (MRA)' and
"Neuroimaging of acute ischemic stroke".)

TREATMENTThere is no treatment proven to be beneficial specifically for lacunar

infarction as opposed to ischemic stroke in general. Most clinical trials investigating
stroke treatment and prevention have failed to adequately separate the lacunar infarct
subpopulation. Nevertheless, the best available evidence suggests that intravenous
alteplase is beneficial for patients with lacunar stroke (see 'Thrombolytic therapy'
below). For secondary prevention, intensive medical treatment is recommended (see
'Prevention' below).

Acute treatment — The assessment and management of the acute phase (ie, the first
few hours) of ischemic stroke is reviewed elsewhere in detail. (See "Initial assessment
and management of acute stroke".)

The main goals in the initial phase of acute stroke management are to ensure medical
stability, begin to uncover the pathophysiologic basis of the neurologic symptoms,
and to determine whether patients with acute ischemic stroke are candidates to receive
treatment with thrombolysis. (See "Intravenous thrombolytic therapy for acute
ischemic stroke: Therapeutic use".)

Thrombolytic therapy — Randomized controlled trials have shown that intravenous

alteplase (recombinant tissue-type plasminogen activator or tPA) improves functional
outcome from ischemic stroke and that benefits outweigh the risks for eligible patients
who receive treatment within 4.5 hours of symptom onset (or within 4.5 hours of
when the patient was last seen normal in cases when onset time is unknown). (See
"Approach to reperfusion therapy for acute ischemic stroke", section on 'Alteplase'.)

Subgroup analysis of trial data suggest that the benefit with thrombolysis is sustained
in patients with lacunar stroke [105]. However, stroke subtype was classified mainly
by clinical impression in the thrombolysis trials since vascular studies usually were
not performed before treatment initiation. Thus, some patients with a large vessel or
cardioembolic stroke mechanism (eg, those with proximal middle cerebral artery
occlusion, good leptomeningeal collaterals, and recanalization after thrombolysis)
may have been incorrectly classified as having a small vessel etiology. Nonetheless,
until better data are available, we recommend that patients with lacunar syndromes be
selected for thrombolysis according to current guidelines in the same way as patients
with other subtypes of ischemic stroke (table 3). (See "Intravenous thrombolytic
therapy for acute ischemic stroke: Therapeutic use".)

Thrombolytic therapy is associated with a 6 percent risk of symptomatic brain

hemorrhage. Thus, its benefits must be viewed with caution in a condition with a
relatively benign natural history (see 'Prognosis' below) [105]. This treatment option
should be discussed with the patient and family in each individual case.

Patients not eligible for thrombolysis — Most patients with acute ischemic stroke who
are not eligible for thrombolytic therapy should be treated with aspirin.
Anticoagulation with heparin is generally not indicated for the management of acute
lacunar stroke. This topic is discussed separately. (See "Antithrombotic treatment of
acute ischemic stroke and transient ischemic attack".)

Prevention — The limited efficacy of acute therapies for lacunar stroke suggests that
secondary prevention should be a major focus of treatment. Intensive medical
intervention and risk factor management, including antihypertensive, antiplatelet, and
statin therapy, is recommended for most patients with ischemic stroke or transient
ischemic attack. (See "Overview of secondary prevention of ischemic stroke", section
on 'Summary and recommendations' and "Antihypertensive therapy to prevent
recurrent stroke or transient ischemic attack".)

The efficacy of aspirin and other antiplatelet agents for preventing second strokes and
mortality has been illustrated for patients with noncardioembolic ischemic stroke in
general (see "Antiplatelet therapy for the secondary prevention of ischemic stroke").
A 2015 meta-analysis identified two trials that evaluated antiplatelets versus placebo
and reported outcomes in the subgroup of patients with lacunar stroke; in the pooled
analysis, treatment with any single antiplatelet agent was associated with a significant
reduction in ischemic stroke recurrence (relative risk 0.48, 95% CI 0.30-0.78) [106].
Therefore, we recommend treatment with an antiplatelet agent for patients with a
history of noncardioembolic stroke or transient ischemic attack of atherothrombotic,
lacunar (small vessel occlusive type), or cryptogenic type. Aspirin, clopidogrel, and
the combination of aspirin-extended-release dipyridamole are all acceptable options
for preventing recurrent noncardioembolic ischemic stroke.

Despite early enthusiasm, results from the SPS3 trial suggest that the long-term use of
combined antiplatelet therapy with aspirin plus clopidogrel is harmful for patients
with lacunar stroke because it leads to an increased risk of hemorrhage and death but
does not reduce the risk of recurrent stroke [107]. Therefore, it should not be
employed for secondary prevention in this population in the absence of proven
indications. The use of aspirin plus clopidogrel for prevention of different subtypes of
ischemic stroke is discussed separately in detail. (See "Antiplatelet therapy for the
secondary prevention of ischemic stroke".)

The Warfarin-Aspirin in Recurrent Stroke Study (WARSS) was a randomized,

double-blind trial that investigated the benefits of aspirin (325 mg/day) compared
with warfarin (international normalized ratio 1.4 to 2.8) in 2206 patients who had an
ischemic stroke within the previous 30 days [108]. Patients scheduled for carotid
endarterectomy or who had a presumed cardioembolic source of stroke were not
included. After two years of follow-up, there was no difference between the two
groups in the prevention of recurrent ischemic stroke or death, or in the rate of major
hemorrhage. More than one-half of the cohort (1237 patients) had a lacunar stroke as
their initial event; this group also demonstrated no difference in outcome between
warfarin and aspirin. Since warfarin does not appear to provide benefit over aspirin,
and is more expensive and more difficult to manage, it does not appear to have a role
in secondary prevention in patients who have had a lacunar infarct, other than in
patients with a presumed embolic source.

PROGNOSISLacunar infarcts have a better short term prognosis than infarcts due to
other stroke mechanisms, at least up to one year after onset.

●A population-based study of 159 patients in Rochester found a case-fatality rate of 0

percent at one month and 3 percent at one year in patients with lacunar infarcts,
compared with 14 and 28 percent, respectively, for nonlacunar infarcts [37].

●In the setting of a controlled clinical trial, 91 percent of patients with lacunar stroke
from the placebo arm had a favorable outcome at three months, as defined by
moderate to good recovery on the Glasgow Outcome Scale [109]. This contrasts with
strokes due to large vessel atherosclerosis; only 55 percent of these patients had a
favorable outcome at three months.

●In a prospective study of 1425 ischemic stroke survivors, patients with lacunar
stroke (n = 234) were more likely to have further neurologic improvement between
three months and one year compared with patients with nonlacunar stroke [110].

However, the longer-term prognosis after lacunar stroke may not differ greatly from
nonlacunar stroke. This observation comes from a systematic review of 19 cohort
studies involving 2402 patients with lacunar and 3462 patients with nonlacunar
ischemic stroke [33]. The odds of death were significantly greater following
nonlacunar than lacunar infarction at one month, 1 to 12 months, and one to five years
(odds ratio [OR] 3.81, 2.32 and 1.77, respectively), although the difference gradually
decreased. However, the odds of recurrent stroke were significantly greater for
nonlacunar infarction only at one month (OR 2.11), and the difference in stroke
recurrence between nonlacunar and lacunar groups was nonsignificant at 1 to 12
months and one to five years.

Analogous findings were reported in a population-based study from Italy [42].

Patients with lacunar stroke (n = 491) had better five-year survival than patients with
nonlacunar stroke (n = 2153), mainly due to lower mortality within the first year of
follow-up for the lacunar stroke group. The lacunar group also had a lower average
annual stroke recurrence rate within the first year. However, stroke recurrence and
mortality rates were similar in the two groups from the second year through study
completion at five years.

Among patients with recent lacunar stroke, factors associated with an increased risk
of ischemic stroke recurrence include a prior lacunar stroke or TIA, diabetes, black
race, and male sex [111]. In addition, the risk of stroke recurrence is increased in the
presence of cerebral microbleeds [112].

Patients with lacunar infarction and more severe initial motor deficits have worse
functional outcome [105,113]. What is not known is whether patients with a lacunar
infarct due to embolism or large vessel atherosclerosis obstructing the ostium of a
penetrator branch have a different prognosis and response to therapy. As long as this
question remains, investigation of the operating stroke mechanism remains important.
(See 'Etiology' above.)

SOCIETY GUIDELINE LINKSLinks to society and government-sponsored

guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Stroke in adults".)

SUMMARY AND RECOMMENDATIONS

●Lacunar infarcts are small (0.2 to 15 mm in diameter) noncortical infarcts caused by

occlusion of a single penetrating branch of a large cerebral artery. These branches
arise at acute angles from the large arteries of the circle of Willis, stem of the middle
cerebral artery, and the basilar artery. Most lacunes occur in the basal ganglia
(putamen, globus pallidus, thalamus, caudate), subcortical white matter (internal
capsule and corona radiata), and pons. (See 'Introduction' above and 'History' above
and 'Vascular anatomy' above.)

●Several mechanisms for occlusion of small penetrator branches have been described
(see 'Etiology' above):

•Lipohyalinosis of the penetrating arteries is the usual cause, particularly of smaller

infarcts (3 to 7 mm in length).

•Microatheroma of the origin of the penetrating arteries coming off the middle
cerebral artery stem, circle of Willis, or distal basilar or vertebral arteries. This
mechanism has been proven pathologically by serial section for the basilar artery.

•In some cases, not proven pathologically, tiny emboli have been suspected as the
cause of these small infarcts.

●Lacunes account for 15 to 26 percent of ischemic strokes. (See 'Epidemiology'

above.)
●Two of the three described mechanisms for lacunar stroke are related to a chronic
vasculopathy associated with systemic hypertension. Other likely risk factors include
diabetes mellitus and possibly smoking. (See 'Risk factors and associations' above.)

●More than 20 lacunar syndromes have been described. Five have been validated as
being highly predictive for the presence of lacunes radiologically (see 'Clinical
features' above):

•Pure motor hemiparesis (see 'Pure motor hemiparesis' above)

•Pure sensory stroke (see 'Pure sensory stroke' above)

•Ataxic hemiparesis (see 'Ataxic hemiparesis' above)

•Sensorimotor stroke (see 'Sensorimotor stroke' above)

•Dysarthria-clumsy hand syndrome (see 'Dysarthria-clumsy hand syndrome' above)

•As a general rule, lacunar syndromes lack findings such as aphasia, agnosia, neglect,
apraxia, or hemianopsia (so-called "cortical" signs). Monoplegia, stupor, coma, loss
of consciousness, and seizures also are typically absent.

●The diagnosis of lacunar infarction in vivo relies upon finding a clinical syndrome
that is consistent with the location of a small noncortical infarct seen on CT or MRI.
Brain imaging with CT or MRI is also useful to exclude other potentially life-
threatening diagnoses such as intracerebral hemorrhage or subdural hematoma.
Investigation of the underlying stroke mechanism (eg, thrombosis versus embolism) is
still indicated to exclude potentially correctable causes of recurrence. (See 'Diagnosis'
above.)

●Intravenous alteplase (recombinant tissue-type plasminogen activator or rt-PA)

improves outcomes for patients with ischemic stroke in general if administered within
4.5 hours of symptom onset. The available evidence suggests that intravenous
thrombolysis is beneficial for patients with lacunar stroke. Most patients with acute
ischemic stroke who are not eligible for thrombolytic therapy should be treated with
aspirin. (See 'Treatment' above.)

●Lacunar infarcts have a better short term prognosis than infarcts due to other stroke
mechanisms, at least up to one year after onset. (See 'Prognosis' above.)