Article Type : Review Article
Authors : De Reuck JL
Keywords : Lacunar syndromes; Lacunar infarcts; Pure motor stroke; Pure sensory stroke; Sensorimotor stroke; Ataxic hemiparesis; Dysarthria-clumsy hand; Prevention; Treatment
Cortical small vessel disease (CSVD) is the main cause of
vascular dementia. However occlusion of a single perforating branch can lead to
a lacunar syndrome (LS). Miller Fisher described 5 types of LSs: a pure motor
stroke, a pure sensory stroke, a sensorimotor stroke and, the ataxic
hemiparesis, and the dysarthria-clumsy hand types. Only the pure motor stroke
had a favourable outcome. LSs are frequently progressive due to the extension
of the occlusion to nearby branches. LSs can also be due to territorial
infarcts in a minority of cases. Treatment modalities are not successful. Only
prevention of the cardiovascular risk factors can slow down the occurrence of
LSs. Mainly early treatment of arterial hypertension is important. Only acute
Intravenous alteplase treatment seems to reduce the severity of the LS.
Lacunar syndromes (LSs)
are due to small deep cerebral infarcts within the territory of a single
perforating artery with a maximum diameter of less than 25 millimetres on
neuro-imaging [1]. Cerebral small vessel disease (CSVD) causes 25% of the
overall number of strokes [2]. The occurrence rate of vascular dementia due to
lacunar strokes is 37% [3]. With an incidence of 15%, it is the second most
important cause of dementia after Alzheimer’s disease [4]. Asymptomatic lacunar
infarcts (LIs) are 5 times more common than symptomatic ones. However, they
must be considered as preceding risk factors for a stroke and cognitive impairment
leading to dementia [5].
In the 1960s, C Miller
Fisher performed autopsy studies showing that vessels supplying LIs display
segmental arteriolar disorganization, characterized by vessel enlargement,
haemorrhage and fibrinoid deposition, that he called “lipohyalinosis” [6].
However, still a minority of LIs is suspected to be due to a cardiac embolic
source or to a symptomatic carotid stenosis [7-9].
CSVD is not only
responsible for LIs but also for ischemic white matter changes [10,11]. Magnetic
resonance imaging (MRI) shows very well the hyperintensive white matter
changes, but probably underestimate the number of LIs [12]. Cerebral
micro-infarcts are overall considered as the invisible lesions on MRI [13]. The
present review will only discuss the LSs due to involvement of a single deep
perforating branch as vascular dementia due to CSVD has been already
extensively been discussed previously [14,15].
On post-mortem
examination LIs, due to CSVD, are most observed in the lentiform nucleus
(100%), followed by the thalamus (70%) and the internal capsule (55%). In the
periventriclar white matter the incidence is 51% and in the caudate nucleus
41%. The lowest frequency is observed in the brainstem (19%) [16]. The
lenticulo-striatal arteries, issued from the middle cerebral artery, supply the
superolateral part of the caudate nucleus, the superior part of the internal
capsule, most of the putamen and partly the globus pallidus. The perforating
branches from the anterior cerebral artery perfuse the medial segment of the
globus pallidus and the inferior part of the internal capsule [17]. The
periventricular white matter is supplied in the fronto-central part of the
brain by ventriculofugal end-branches of the lateral lenticulo-striatal
arteries, while in the parieto-occipital regions it is supplied by
ventriculofugal branches issued from the choroidal arteries [18]. The thalamus
is mainly supplied by performing branches, issued from the basilar artery, and
from the posterior communicating and posterior cerebral arteries [19]. On
post-mortem angiograms the deep perforating arteries are poorly filled and show
several narrowing’s and post-stenotic dilatations in brains with LIs. A
responsible occlusion is observed in 80% of the lesions [20].
CSVD is predominantly
observed in aged patients with a strong previous history of early occurring
adulthood vascular risks [21]. Arterial hypertension is the most established
vascular risk factor for the occurrence of CSVD [22]. The incidence of white
matter lesions is less severe in hypertensive adults with well-treated arterial
hypertension compared to those in which the treatment was less severe and less
well followed up [22]. Increased body mass index, cardiovascular disease, lack
of physical activity, heavy alcohol consumption, smoking, hypercholesterolemia
and diabetes are considered as additional risk factors when already occurring
in young adulthood [23]. Atrial fibrillation and carotid stenosis are
associated more with non-lacunar than with lacunar infarction [24]. Hyperhomocysteinemia
has also been considered as an increased risk of LIs in the basal ganglia [25].
Miller Fisher described
five types of classical clinical syndromes: pure motor stroke, pure sensory
stroke, sensorimotor stroke, ataxic hemiparesis, and dysarthria-clumsy hand
[26]. On MRI with diffusion-weighted imaging performed within 5 days after the
appearance of the LS, only pure motor stroke correlated with the presence of
the LI in the controlateral posterior limb of the internal capsule. In the
other syndromes no clinico-neuroimaging correlation was observed [27]. Pure
motor hemiparesis is observed in 57% of the LSs. Sensorimotor syndrome in 20%,
ataxic hemiparesis in 10%, pure sensory syndrome in 7% and dysarthria-clumsy
hand syndrome in 6% are the incidences in the remaining types [28]. The pure
motor stroke involves to the same degree the face, the arm and the leg.
Although the main location is the internal capsule, a minority is due to a
pontine lacuna. The long-term prognosis is excellent with in the majority of
cases a complete recovery within six months [29].
The pure sensory stroke syndrome is difficult to
delineate because the symptoms are mainly subjective, linked to the thalamus
[30]. Also cases of pure sensory stroke due to a pontine lacunes have been
described [31,32]. Sensorimotor stroke is the most difficult defined LS as
additional cortical signs cannot always been excluded clinically. Both equal
sensory and motor involvement of the face, the arm and the leg with exclusion
of cortical participation have to be confirmed mainly by neuroimaging
techniques [33]. The atactic hemiparesis syndrome presents with cerebellar
ataxia and with pyramidal signs involving the limbs at the same side [34]. The
LI is limited to the basis pontis, opposed to the clinical symptoms [35]. Dysarthria-clumsy
hand syndrome has similarities with the atactic hemiparese syndrome: moderate
weakness of the face, and upper and lower limbs, moderate dysarthria and
dysmetria, Babinski sign and, slight dragging and imbalance of the leg on the
right side. Fisher found a 5 mm lesion in the pons on the side opposed the
clinical deficit [36]. Also other sides have been observed [37,38]. Pseudo-lacunar
syndromes have as well been described. However the extreme variety of the
symptoms makes their inclusion as LSs highly improbable [39].
When comparing visible
symptomatic LIs on CT scans the average size of the lesions is smaller in the
independent patients compared to in those with a remaining handicap. The LI
decreases in average size from day 3 to 10 in the former group but remains
unchanged in the group of still disabled patients [40]. LSs are a major cause
of progressive motor deficits, probably because of stepwise occlusion of the
branches of small perforating arteries [41]. LIs are more frequently
progressive than large artery disease and cardio-embolism. Their pattern varies
according to the location of the LI [42]. However, the main risk in patients
with LIs is the progressive cognitive impairment, eventually leading to
vascular dementia [43]. From the onset on LIs are associated with a moderately
increased overall mortality compared to the normal general population.
Post-stroke mortality risks from LIs associated to atherothrombotic and
cardio-embolic strokes are significantly higher [44]. The mortality rate after
a mean follow-up of 3.6 years is 1.78% [45].
Prevention and Treatment
The most widely accepted
approach to prevention and treatment is to intensively control of the
well-established vascular risk factors, of which arterial hypertension is the
most important [2]. Antithrombotic treatment with aspirin has not been
effective in the long-term lacunar stroke prevention and treatment [46]. Addition
of clopidogrel did not reduce the risk of recurrent LS [47]. However, it
significantly increases the risk of bleeding and death [48]. Aspirin plus
extended–release dipyridamole also is not found to be very effective [49]. On
the other end, an effective treatment with intravenous alteplase in patients
with imaging-defined acute LAs is observed, similar to those experienced in other
subtypes [50]. Oral anticoagulants and left atrial appendage closure do not
prevent recurrence of single LIs [51].
Lis not due to CSVD
represent between 16 and 20% of patients with a LS history. They are mainly the
result of embolism due to atrial fibrillation [52,53]. Seizures are not
observed in patients with pure LSs [54, 55]. When occurring they only reflect
the existence of an underlying neurodegenerative process that is responsible
for mental deterioration [56]. Another disease with LIs and severe white matter
changes is the cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL) due to Notch3 mutation [57].
However, in this disease only mild gait disturbances are associated to the
vascular cognitive deterioration [58].
Positron emission
tomography (PET) can already demonstrate a global decrease of cerebral blood
flow in patients with silent LIs [59]. No PET studies are available in patients
presenting a solitaty LS. However, cerebral blood flow is lower in the cerebral
cortex and the white matter of subjects with intensive white matter
hyper-intensities on MRI [60]. In our study LSs due to LIs only represent 11%
of the whole stroke population [27] instead of the 25% observed in a more recent
study [27].
The authors have nothing
to declare in relation to this article. No funding was received for the
publication of this article.