Perspectives in Medicine (2012) 1, 214217

Bartels E, Bartels S, Poppert H (Editors):

New Trends in Neurosonology and Cerebral Hemodynamics an Update.
Perspectives in Medicine (2012) 1, 214217

journal homepage: www.elsevier.com/locate/permed

The contribution of microembolic signals (MES)

detection in cardioembolic stroke
Martin A. Ritter

Department of Neurology, University Hospital of Mnster, Mnster, Germany

KEYWORDS
Microembolic signals;
Atrial brillation;
Left ventricular assist
devices;
Cardioembolic stroke
Summary
Background: Cardioembolic stroke accounts for about one third of all strokes. Microembolic
signals (MES) are frequently found in patients with acute stroke. The role of MES in cardioembolic
stroke is less well investigated.
Methods: Medline based literature review of clinical trials linking MES and stroke with cardiac
sources of various risks.
Results: MES are a rare nding in patients with cardioembolic stroke as well as in sources
of potential cardiac embolism (e.g. myocardial infarction, atrial brillation, left ventricular
thrombus). The low number of patients with MES and the low number of MES during the inves-
tigation times leads to a limited statistical power of positive and negative ndings. MES in
patients with articial heart valves and the DeBakey left ventricular assist device (LVAD) are
predominantly gaseous and do not correlate with stroke risk. In patients with the Novacor LVAD,
MES strongly correlate with stroke risk.
Conclusion: Currently, the role of MES in cardioembolic stroke is only limited due to both, the
low prevalence of MES and the number of MES per investigation. Larger studies would be needed
to strengthen this role.
2012 Published by Elsevier GmbH. Open access under CC BY-NC-ND license.

Background rhythm disturbances with high embolic risk such as atrial

Cardioembolic stroke accounts for about one third of all
strokes. In some registries, percentages even reach 40%. The
diagnosis of cardioembolic stroke requires that alternative
stroke etiologies have been ruled out comprehensively. Diag-
nosis of cardiac embolism thus usually requires the presence
of a structural abnormality of the heart or the diagnosis of
Correspondence address: Department of Neurology, University of
Mnster, Albert-Schweitzer-Campus 1, Gebude A1, D-48149 Mn-
ster, Germany. Tel.: +49 251 8345536; fax: +49 251 8348181.
E-mail address: Martin.Ritter@ukmuenster.de
brillation (AF) [1].
According to general consensus, cardiac lesions can be
divided into high risk and low or uncertain risk of sub-
sequent embolism [2]. The differentiation is of considerable
importance, as the therapeutic regimen to prevent future
embolism varies between different embolic risks. Table 1
gives an overview of high and low risk lesions.
Even without proving a cardiac source, some features of
an acute stroke give clues to a cardiac source of stroke.
For example, patients with cardioembolic stroke frequently
have clinically more severe stroke than others, frequently
decreased level of consciousness, and severe cortical symp-
toms such as neglect or aphasia [2]. On cerebral imaging
especially multiple lesions in different arterial territories

2211-968X 2012 Published by Elsevier GmbH. Open access under CC BY-NC-ND license.
doi:10.1016/j.permed.2012.02.031
MES detection in cardioembolic stroke 215

Table 1 High and low risk lesions for cardiac embolism [2]. Table 2 Prevalence of MES in various stroke etiologies.

High risk Low risk Author, year Large artery Cardioembolic Small vessel
embolism stroke n/N % disease n/N
Atrial Atrial
n/N, % %
Atrial brillation Patent foramen ovale
Atrial utter Atrial aneurysm Idicula, 4/13, 30% 4/7, 36% 0/2, 0%
Sick sinus syndrome Spontaneous echo 2010 [4]
contrast Poppert, 20/103, 20% 5/143, 3.5% 0/147, 0%
Left atrial thrombus 2006 [5]
Left atrial myxoma Serena, 8/39, 20% 6/35, 17% 0/64, 0%
2000 [6]
Ventricular Ventricular
Kaposzta, 10/20, 50% 1/22, 4% 0/20, 0%
Left ventricular Dyskinetic wall
1999 [7]
thrombus segments
Daffertshofer, 18/105, 4/65, 6.2% 3/67, 4.5%
Left ventricular myxoma Hypertrophic
1996 [8] 17.1%
cardiomyopathy
Sum 60/280, 21% 20/272, 5% 3/300, 1%
Recent myocardial Congestive heart failure
infarction
Dilated cardiomyopathy
prevalence of MES was generally low. The lowest percentage
Valvular Valvular was found in the largest study of Poppert and colleagues,
Mitral stenosis Lambls excrescences nding MES in only ve of 143 (3.5%) patients with cardiac
Prosthetic valves Fibroelastoma embolism [5]. The overall prevalence of MES in patients with
Infective/non-infective Mitral-valve prolapse cardio-embolic stroke is about 5%. No study found MES to be
endocarditis predictive of recurrent cardioembolic stroke, which could
also be the effect of the low case numbers with MES and the
restricted observation times.
strongly favours a cardiac source of embolism. Furthermore, Ferro commented in his paper that cardioembolic stroke
microembolic signals (MES) detected in both middle cere- should be assumed in case MES are found bilaterally [2].
bral arteries make a proximal source of embolism, mainly However although this assumption is quite plausible, its clin-
the heart, very likely [2]. ical relevance is very low. First, as mentioned above, only
Microembolic signals (MES) are frequently found in a minority of patients with cardioembolic stroke will have
patients with acute stroke and especially in those with MES at all. Second, the number of MES per investigation is
symptomatic carotid stenosis [3]. The role of MES in car- very low (about 1 or 2 MES per hour). Finding larger numbers
dioembolic stroke is less well investigated. The following of MES is rare. However, bilateralism cannot be assumed in
overview will highlight the current role of MES detection case of only one MES per session and even with two signals
in the diagnosis and therapy of various sources of cardiac during the session there is still a 50% chance that these two
embolism. signals occur on the same side of the brain.
Furthermore, bilateral MES can also be found in cases
Methods with artery to artery embolism. Poppert et al. found in his
study bilateral MES in 3 of 20 patients with this stroke etiol-
ogy [5]. In one patient, contralateral carotid occlusion may
Medline listed studies were identied by the following
have accounted for this nding, but no obvious reason was
search terms: MES OR ES OR HITS AND Cardia*
depicted in two cases. In summary, MES are an infrequent
OR heart OR atri* OR ventri*. Studies were
nding in cardioembolic stroke, MES detection does thus not
selected upon relevance to the subtitles of the following
contribute to the work-up of unselected stroke patients to
overview. If appropriate, data from different studies were
determine stroke etiology.
grouped in tables and commented in context.

MES in cardiac disease with a risk of stroke

Prevalence of MES in patients with cardioembolic
stroke
There are a number of studies investigating the prevalence
of MES in unselected stroke cohorts. An overview on the
studies comparing the prevalence of MES in detailed stroke
etiologies according to TOAST criteria is given in Table 2.
In a recent study, Idicula found quite a high prevalence
of MES in patients with cardiac embolism that even topped
the prevalence found in patients with symptomatic carotid
stenosis [4]. However, in this study, only 40 patients had
been included in total and MES were found in four of eleven
patients with cardiac embolism. In the larger studies the
This paragraph will look at cardiac embolism from the other
side of the medal. What does MES detection contribute
to the patients work-up in case there are known cardiac
lesions and the investigator wants to address the risk of
future stroke.
MES after myocardial infarction
Stroke is a possible complication of acute myocardial infarc-
tion and affects 23% of patients with acute coronary
syndromes (ACS) [9]. The risk to suffer stroke within the
216
Table 3 Prevalence of MES in various sources of cardiac
embolism [12].
Cardiac pathology n Prevalence of MES
Infective endocarditis 7 43%
Left ventricular aneurysm 38 34%
Intracardiac thrombus 23 26%
Dilated cardiomyopathy 39 26%
Non-valvular atrial brillation 24 21%
Valvular disease 80 15%
Prosthetic heart valves 89 55%
Overall 23% (without
prosthetic heart
valves)
30 days after myocardial infarction is about 10 times higher
than before and thereafter. It is therefore reasonable to use
MES detection as a predictor of future stroke in this setting.
Nadareishvili et al. found MES in 17 of 100 patients within
72 h from onset of an acute coronary syndrome [10]. MES
were more frequently found in patients with LV thrombus,
akinetic left ventricle and decreased ejection fraction on
echocardiography. They also found that during the follow-
ing days 3 patients suffered stroke, all of which had MES at
baseline [10].
Unfortunately, these results could not be reproduced in
a recent study from Spain, in which 209 patients with ACS
had been investigated with a very similar protocol [11]. The
authors found MES in only 7 patients (prevalence of 3.4%)
and patients were followed for 14 months. In the follow-
up period, only 3 patients had a subsequent stroke, none
of them had MES at baseline. Apart from stroke, no other
vascular event could be predicted by the presence of MES.
Overall, the data are thus inconclusive, again in part due
to the low prevalence of MES in this cohort and the low
overall case number in the studies. From a practical point
of view, MES detection does not seem to be very helpful in
predicting stroke after ACS.
MES in other cardiac sources of embolism
Georgiadis et al. reported in his milestone paper on this
subject the prevalence of MES in 300 patients with vari-
ous cardiac sources of embolism [12]. The detailed numbers
are given in Table 3. The highest prevalence was found for
patients with infective endocarditis, the lowest for chronic
valvular disease. No associations could be found for MES and
patients age or sex or actual medication. Only high risk once weekly for 30 min, and thromboembolic events were
lesions according to Table 1 were investigated. Although
the study was quite large, no data on patient outcome and
the risk of future stroke for patients with and without MES
are given. Thus, for most of the sources prospective studies
would be needed to determine the role of MES detection to
predict future cardioembolic stroke.
MES in atrial brillation
Atrial brillation is the single most frequent cause of car-
dioembolic stroke. No wonder MES detection has been used
M.A. Ritter
in a number of studies in this entity. Studies have tried to
determine the prevalence of MES, the risk of patients with
MES to suffer subsequent stroke and to correlate the pres-
ence of MES with anticoagulation therapy.
In the paper of Georgiadis et al., 5 of 24 patients (21%)
with atrial brillation (AF) had MES [12]. Nabavi et al. found
MES in 11 of 26 patients (42%) with valvular AF compared
with 3 of 21 patients (21%) with non-valvular AF [13]. MES
were also more frequently found in patients with a history
of thromboembolism. Cullinane et al. found MES in 13 of
86 patients with non-valvular AF (15%) [14]. There was no
difference in the prevalence between symptomatic (16%)
and asymptomatic (13%) patients. Furthermore, there was
no correlation between MES and the use of aspirin or left
atrial thrombus. There was also no correlation between
MES and echocardiographic risk markers (such as left atrial
enlargement). One study investigated, whether MES were
more frequent in 37 patients with stroke due to AF compared
with 10 patients with AF but without stroke and 92 controls
[15]. MES were detected in 11 (29%) of the symptomatic
patients and only in one without a history of stroke. The
MES count was quite high in this study with 15 events per
hour which sheds some doubt on the credibility of the data.
Over a follow-up period of 18 months one patient with MES
at baseline had a recurrent stroke; however this occurred
1 year from study inclusion.
Overall, studies were too small to address the question
of stroke risk and studies are too heterogeneous to perform
a meta-analysis of studies performed. Until larger studies
report otherwise, there seems to be no added value of MES
detection to address clinical questions in patients with AF.
MES and left ventricular assist devices
MES detection is a well-established method to monitor car-
diac or vascular procedures. Currently, a well-established
procedure is the implantation of cardiac left ventricular
assist devices (LVAD) that allow bridging of patients
with very severe left ventricular cardiac failure to heart
transplantation or until the heart has recovered from a
temporary disease. These patients are constantly endan-
gered by the occurrence of systemic and frequently cerebral
embolism although antiplatelet and anticoagulation strate-
gies are both used to decrease this risk. These patients are
well characterised and an attractive group of patients to
test whether silent microembolism is associated with clini-
cal events. In one study, 20 patients with the Novacor N100
LVAD were investigated [16]. MES detections were performed
recorded. 44 events occurred in 3876 LVAD days resulting
in an incidence of 1.1% events per day (400%/year). The
overall MES prevalence was 35.3% with a median MES num-
ber of 2.3/h. There was a strong correlation between MES
activity and incidence of thromboembolism and times with
events were predicted by MES activity with a moderate
positive predictive value (0.370.7) and a high negative
predictive value (0.821.0). Concerning therapy, patients
on both medications, oral anticoagulants and antiplatelets,
had less events (0.7% vs. 2.8%) and a lower MES prevalence
(18.3% vs. 65.4%) than patients on anticoagulation alone.
Therefore, MES detection seems very useful in patients with
MES detection in cardioembolic stroke
the Novacor device as it correlates with therapy and clini-
cal events. In another study patients with the DeBakey were
investigated [17]. 23 patients were monitored twice weekly
with and without oxygen inhalation. Therapy and documen-
tation of clinical events was identical to the rst study.
In these patients the embolic risk of 0.24%/per day was
80% less than for patients with the Novacor LVAD, although
the prevalence of MES (35.1%) was the same as in Novacor
patients and the number of MES was much higher (mean
81 443/h) than in the Novacor device. The authors found
no correlation between MES activity and incidence of throm-
boembolism or hemostatic treatment for patients with the
DeBakey device. The authors also found that the number of
MES with the DeBakey device decreased signicantly after
oxygen inhalation suggesting a gaseous nature of most of the
MES in patients with the DeBakey device. Gaseous MES have
been shown to not correlate with stroke risk, something that
has been observed with articial heart valves in the past.
Sliwka and Georgiadis retrospectively evaluated 369
patients with various types of articial heart valves
>3 months concerning the risk of stroke and the presence
and number of MES [18]. They found signicant differences
in MES prevalence and counts depending on valve type.
Although the prevalence of MES ranged from 9% (biological
valves) to 92% (Bjrk Shiley) and the average MES numbers
from 0 to 133 per hour there was no association between MES
counts and INR, age, cardiac rhythm, and implant duration.
There was also no predictive value of MES for a history of
neurological symptoms which were prevalent in 42 patients.
In summary, MES detection seems useful in patients with
Novacor LVAD to guide therapy and to predict clinical events.
However this does not hold true for patients with the
DeBakey LVAD and not for patients with articial heart valves
as most MES in these patients are from gaseous nature.
Conclusion
MES are an infrequent nding in most cardiac sources of
embolism and due to the low case numbers in most stud-
ies and the low absolute number of MES any conclusion
is premature. Much larger studies would be needed with
homogeneous study populations to address most questions
covered in this review, especially to monitor therapeutic
effects or to predict future strokes. From a pragmatic point
of view, there is currently no established role of MES detec-
tion in cardiac embolism.
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