An unexpected evolution of symptomatic mild
middle cerebral artery (MCA) stenosis:
asymptomatic occlusion
Malferrari et al.
Malferrari et al. BMC Neurology 2011, 11:154
http://www.biomedcentral.com/1471-2377/11/154 (13 December 2011)

Malferrari et al. BMC Neurology 2011, 11:154
http://www.biomedcentral.com/1471-2377/11/154

CASE REPORT

Open Access

An unexpected evolution of symptomatic mild
middle cerebral artery (MCA) stenosis:
asymptomatic occlusion
Giovanni Malferrari1†, Marialuisa Zedde1*†, Gianni De Berti2†, Massimo Maggi2† and Norina Marcello1†

Abstract
Background: The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke
in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been
reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause
of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial
steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement
is highly dynamic in both directions, improvement or worsening, although several data are derived from the
atherosclerotic subtype, compared to other causes.
Case description: We report the clinical, neurosonological and neuroradiological findings of a young woman, who
came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological
examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging
confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was
significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective
cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipidlowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our
attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but
the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.
During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination
found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging
did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the
left M1 MCA occlusion.
Conclusions: Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial
stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at
our knowledge.

Background
It has been known since several years that ischemic
stroke related to large intracranial arteries steno-occlusion has a poor prognosis, if the vessel recanalization
does not occur within 1 hour [1]. Indeed M1 MCA
* Correspondence: zedde.marialuisa@asmn.re.it
† Contributed equally
1
Neurology Unit, Department of Neuromotor Physiology, Azienda
Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Viale
Risorgimento 80, 42100 Reggio Emilia, Italy
Full list of author information is available at the end of the article

occlusion is recognized to be a very harmful condition
with an unfavorable outcome. Several papers reported
the rate and course of both symptomatic and asymptomatic intracranial stenosis and the dynamic progression
of a symptomatic atherosclerotic MCA stenosis has
been well described as a risk factor for stroke recurrence
[2,3]. Conversely, only few data are available about
asymptomatic intracranial occlusions and, at our knowledge, it is the first report of an asymptomatic main stem
MCA occlusion, as evolution of a MCA stenosis.

© 2011 Malferrari et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Malferrari et al. BMC Neurology 2011, 11:154
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Case description
A 26 years-old woman came to our attention because of
the abrupt onset of aphasia during her work (she was a
lower school teacher). This symptom lasted several days
with a progressive improvement during hospital staying
and a final complete recovery. The patient arrived in the
Emergency Department four hours after the onset of
symptoms and an unenhanced brain CT did not show
abnormalities. Urgent blood tests was also normal. The
neurological evaluation reported a mild aphasia with
prevalent anomic and paraphasic alterations, without
motor deficits; the National Institute of Health Stroke
Scale (NIHSS) score was 1.
At this point an urgent neurosonological study was
performed both in the extracranial and intracranial vessels, showing a normal appearance of the extracranial
carotid and vertebral axis and a suspected left distal M1
MCA stenosis, by using unenhanced Transcranial Colour-Coded Sonography (TCCS). Therefore, because of
the suboptimal temporal bone window, contrastenhanced TCCS was performed by intravenous injection
of sulphur hexafluoride (Sonovue ®). It confirmed the
presence of a left distal M1 MCA stenosis; moreover
this finding was congruent with signs and symptoms of
the patient. The ultrasound grading of the MCA stenosis was performed according to the Baumgartner’s velocity criteria [4], and the stenosis was evaluated as ≥ 50%
(Figure 1, row A). The left M2 MCA waveform did not
show an abnormal pattern, also compared with the contralateral corresponding segment. The left A1 anterior
cerebral artery (ACA) did not show signs of flow diversion and the posterior cerebral artery (PCA) waveform
appeared normal.
Subsequent brain Magnetic Resonance Imaging (MRI)
showed a left caudate head and temporal cortical
ischemic damage and the Magnetic Resonance Angiography (MRA) confirmed the left MCA stenosis (Figure
1, row A).
The past medical history of the patient was significant
only for a previous diagnosis of hyperinsulinemia, treated with metformine; overwheight is present (BMI 26).
The diagnostic pathway included blood testing and
instrumental evaluation to rule out a primary or secondary central nervous system vasculitis. An accurate anamnestic survey was performed about the previous
occurrence of any event that could point to immunological and/or rheumatologic or infectious processes, with
negative results. Blood samples were taken for screening
of autoimmune diseases and common acquired or congenital thrombophylic factors or coagulation abnormalities, both with negative findings. The titration of
autoantibodies did not show any abnormality, also
including antiphospholipid and anti-beta2 glycoprotein 1
antibodies. Serological screening for borreliosis,

Page 2 of 5

herpesviruses (comprising Varicella-Zoster virus - VZV)
and influenza viruses was not suggestive for a first or
recurrent infection. Also the lymphocyte typing and the
immunofixation electrophoresis of immunoglobulins
were normal.
Antiplatelet and HMGCoA reductase inhibitor therapy
was early started and a selective Digital Subtraction
Angiography (DSA) was proposed, but the patient initially refused it.
After 20 days the patient was again evaluated because
of the recurrence of a ten minutes-lasting episode of
aphasia. Both neurosonological and neuroradiological
examinations were repeated and their findings were
unchanged; at this point the patient agreed to undergo
selective DSA of the cerebral vessels. Therefore DSA
was performed after 10 days. Meanwhile a dual antiplatelet therapy with acetyl salicylic acid and clopidogrel
was suggested. The DSA findings (Figure 1, row B) was
similar to TCCS and MRA results for the identification
of the left distal M1 and M2 MCA branch stenosis, but
the angiographic grading (50%) was lesser than the
expected one.
In the following ten months no other event has been
reported by the patient and she was phone called in
order to undergo a contrast-enhanced TCCS as a follow-up test. TCCS was performed in second harmonic
imaging with pulse inversion and sulphur hexafluoride
(Sonovue®) 2.5 mL was injected by the right antecubital
vein. A left M1-M2 MCA occlusion was diagnosed, with
a large early branch, arising from the M1 MCA segment
just before the stop (Figure 1, row C). This findings
were really unexpected and therefore a brain MRI and
MRA were performed, showing respectively the lack of
new brain parenchymal lesions with a normal perfusional status, and an absent flow signal in the left M1M2 MCA. Moreover this last finding was confirmed by
a subsequently performed DSA, also viewing the early
M1 MCA branch that vascularizes the distal MCA territories (row C of the Figure 1 lists the follow-up neurosonological and neuroradiological data).
In the following 16 months neurosonological control
examinations overlapped the last findings and no neurological event was reported. Also neuropsychological testing was normal and the patient was treated with a
Serotonine Selective Reuptake Inhibitor, because of an
associated post-stroke depression.

Discussion
This case, during its course, raises some relevant discussion points to be clarified during the clinical reasoning.
First, the infarction localization at the caudate nucleus
is seldom documented in the literature in case of MCA
stenosis [5,6]. This location of ischemic damage was
found congruent with the MCA territory, because the

Malferrari et al. BMC Neurology 2011, 11:154
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Page 3 of 5

Figure 1 Neuroimaging data of the patient. The neurosonological and neuroradiological findings are shown. Row A refers to the first
occurrence of stroke. 1. TCCS image with contrast agent from the left temporal bone window in the mesencephalic axial plane (power mode).
The red dot points to the left M1 MCA, with the corresponding flow spectrum. 2. MRA with TOF reconstruction: the red dot points to the left
MCA stenosis. 3. T2-weighted MRI with the caudate head lesion 4. Corresponding positive DWI-MRI 5. T2-weighted MRI with cortical sulcal
damage 6. Corresponding positive DWI-MRI. Row B shows: 1. DSA images of right and left MCA, with the confirmed mild left M1-M2 stenosis. 2.
T2-weighted MRI of the left hemisphere with the signs of the previous infarction. 3. corresponding negative DWI-MRI. Row C refers to the third
neuroradiological and neurosonological control examinations. 1. TCCS image with contrast agent from the left temporal bone window in the
mesencephalic plane (Power mode), showing the left main stem MCA stop, and the early MCA branch. 2. Corresponding schematic drawing. 3.
The Doppler waveform of the left A1 ACA is showed (the red dot points on the corresponding vessel segment in the Power-mode TCCS image),
and the increased flow velocity suggests a condition of flow diversion for contributing to the reperfusion of MCA territory. 4. TOF MRA
reconstruction with absent signal from left M1 MCA. 5. MRA source image with the proximal left M1 MCA branch, nearest to the origin of the
vessel, coursing along the silvian fissure (white arrow); see for comparison the normal right MCA in the same figure. 6. DSA image, showing a
good correspondence with the neusonological findings, comparing the right and the left MCA. 7. Zoomed detail of the very early left MCA
branching (yellow arrow) on DSA, just before the MCA occlusion, nearest to the carotid bifurcation (white arrow).8. 8, 9, 10 Temporal sequence
of selective DSA with contrast injection in the left. 9. ICA, showing the slow reperfusion of the distal MCA territories by the early. 10. MCA
branch and the contribution of the anastomosis with distal branches of the left ACA..

Malferrari et al. BMC Neurology 2011, 11:154
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lateral lenticulostriate arteries, arising from the M1
MCA, are known as main feeders of the caudate territory [7]. In this context the stroke can be classified,
from the etiological point of view, as a parent artery disease (PAD) subtype of lacunar infarctions and the distal
location of the MCA stenosis in the M1 segment agrees
with the caudate site of the ischemic damage [8]. This
subtype of lacunar stroke is caused by a large artery
intracranial disease and it shares the prognosis with the
large artery atherosclerosis subtype of stroke, i.e. a
higher risk of recurrence than lacunar subtype caused
by small vessel disease [9,10].
Second, the difference in the grading of the MCA stenosis between TCCS and DSA was somewhat surprising
initially, and we have not a definite explanation about
this single case from the literature data. It is possible
that a high flow condition was present in order to maintain a sufficient perfusion downstream the stenosis and
to sustain the collateral circulation. A similar situation
has been seldom demonstrated in the post-acute phase
of striato-capsular infarction, although it was considered
a transient phenomenon [11]. The time interval between
TCCS (Figure 1, row A) and DSA seems not to be
responsible of this difference in grading, in our opinion,
because a control TCCS was performed 24 hours after
the DSA examination and the neurosonological grading
was substantially unchanged.
The third but maybe more relevant point is the course
of the vessel lesion, dramatically worsening, associated to
a clinical silence. The asymptomatic course can help to
explain the difference in grading, discussed above,
because of the efficient recruitment of collateral channels, of which the high flow velocity of the left MCA at
the site of the stenosis may be a marker. Several previous
studies showed that intracranial atherosclerosis is an
highly dynamic process, reporting both progression or
regression by using neuroradiological [2] and neurosonological [3,12] techniques. The conclusion of all studies is
that the progression of a symptomatic MCA stenosis is a
strong predictor of a poor outcome and an independent
predictor of stroke recurrence [13]. Therefore the evolution of the present case is really unexpected, both from
the vascular perspective and from the clinical one.
In the case series of Kern and colleagues [14] only two
patients were reported to have an asymptomatic MCA
occlusion, but without information about the previous
condition of the vessel. The evolution in the present
case was quite different, and the same study [14] concluded that “progression from stenosis to occlusion was
not observed” in 102 consecutive patients with atherosclerotic MCA disease.
The evolution of the MCA stenosis in our case was not
previously described in the literature, at our knowledge,
not only for intracranial atherosclerotic stenosis but also

Page 4 of 5

for other causes of intracranial vessel disease. Diagnostic
investigations about the causes of the MCA stenosis in
our patient were substantially negative and the neuroradiological findings were not pathognomonic for vasculitis, dissection or a moiamoia disease, although this last
condition can be very challenging in the initial phase and
a longer follow-up could allow to identify the involvement of other intracranial vessels. At the moment, however, a clear definition about the causes of the MCA
stenosis has not been reached in our case.

Conclusions
It is possible that inflammatory and metabolic factors,
potentially related to each other, have played a role in
the evolution of the vessel history, but both vascular
and clinical course of this case are previously unreported in the neurological literature at our knowledge.
Consent
Written informed consent was obtained from the patient
for publication of this case report and any accompanying images.
Author details
1
Neurology Unit, Department of Neuromotor Physiology, Azienda
Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Viale
Risorgimento 80, 42100 Reggio Emilia, Italy. 2Department of Neuroradiology,
Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico,
Viale Risorgimento 80, 42100 Reggio Emilia, Italy.
Authors’ contributions
GM revised the draft and performed the first ultrasound evaluation; MZ
wrote the draft and performed the follow-up of the patient; GDB revised the
neuroradiological examinations and co-revised the draft; MM performed the
neuroradiological follow-up and co-revised the draft; NM revised the draft.
All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 28 August 2011 Accepted: 13 December 2011
Published: 13 December 2011
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Pre-publication history
The pre-publication history for this paper can be accessed here:
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Cite this article as: Malferrari et al.: An unexpected evolution of
symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic
occlusion. BMC Neurology 2011 11:154.

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