672

J Neurol Neurosurg Psychiatry 2001;70:672–674

SHORT REPORT

Massive haemorrhagic transformation in
cardioembolic stroke: the role of arterial wall
trauma and dissection
G R de Freitas, A Carruzzo, A Tsiskaridze, J A Lobrinus, J Bogousslavsky

Abstract
The pathogenesis of massive haemorrhagic
transformation is not well established.
Fatal haemorrhagic transformation associated with in situ dissection after acute
middle cerebral artery (MCA) occlusion in
a patient with atrial fibrillation is reported.
An 80 year old woman with atrial fibrillation developed mild hemiparesis and aphasia. Brain CT and MRI at 4 and 5 hours,
respectively, of symptom onset showed
proximal MCA trunk occlusion with developing striatocapsular infarct and hypoperfusion in the superficial MCA territory. A
few hours later, she developed massive
bleeding into the ischaemic area and died.
Pathological examination showed MCA
trunk dissection, surrounded by a subarachnoid clot which communicated with
the cerebral haematoma. It is suggested
that direct arterial wall trauma as a result
of cardioembolic MCA occlusion caused
bleeding into the infarct. Secondary in situ
dissection may be an overlooked mechanism of haemorrhagic transformation.
(J Neurol Neurosurg Psychiatry 2001;70:672–674)

Keywords: cerebrovascular diseases; haemorragic transformation; cardioembolic stroke; intracranial dissection

Haemorrhagic transformation can be a devastating complication of ischaemic stroke.
Moreover, as it is the main complication of
thrombolytic treatment, a clear understanding
of its pathogenesis is essential. Several mechanisms have been proposed, but several issues
remain unresolved.1 2 We have previously suggested that vascular rupture might play a part
in haemorragic transformation.3 We describe a
patient with atrial fibrillation who presented a
fatal intrainfarct haematoma associated with in
situ dissection after acute middle cerebral
artery (MCA) occlusion.
Case report
An 80 year old woman, known to have atrial
fibrillation, was treated for arterial hypertension. Six years previously she had needed
emergency abdominal surgery for mesenteric
ischaemia. She was not currently receiving
prophylatic oral anticoagulants. On the morning of admission to hospital, she collapsed in

Department of
Neurology, Centre
Hospitalier
Universitaire Vaudois,
Lausanne, Switzerland
G R de Freitas
A Carruzzo
A Tsiskaridze
J Bogousslavsky
Department of
Pathology
J A Lobrinus
Correspondence to:
Professor J Bogousslavsky
Julien.Bogousslavsky@
chuv.hospvd.ch
Received 24 March 2000 and
in revised form
12 September 2000
Accepted 11 October 2000

Figure 1 DiVusion weighted (left) and perfusion weighted (right) brain MRI 5 hours after the onset of symptoms. Note
(1) the lesion in the left basal ganglia and centrum semiovale and (2) global hypoperfusion in the left middle cerebral
artery territory.

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673

Massive haemorrhagic transformation in cardioembolic stroke

Figure 2 (A) Horizontal brain section disclosing a large haematoma centred in the left basal ganglia, with massive
intraventricular haemorrhage. (B) Transverse section of the M1 segment of the left middle cerebral artery (van
Gieson-elastin), showing an atheromathous plaque with fresh haemorrhage and dissection between the intimal plaque and
the media (arrow), and extension of the blood through the media to the adventitial region (arrowhead). Note the fresh
thrombotic material in the lumen.

the bathroom and was found unconscious.
Neurological examination in the emergency
room showed non-fluent aphasia without
spared comprehension, a mild proportional
right motor hemisyndrome, and no clouding of
consciousness. Two hours later, the paresis
evolved to plegia and she presented a right sensory hemisyndrome, a left conjugate ocular
deviation, and aphemia. Brain CT, performed
4 hours after the initial symptoms appeared,
showed eVacement of sulci and MCA trunk
occlusion. DiVusion weighted MRI, carried
out 1 hour later, showed a lesion in the left
basal ganglia and centrum semiovale, and perfusion weighted MRI showed global hypoperfusion in the superficial MCA territory (figure
1). The mean arterial blood pressure was 120
mm Hg. The patient was given low dose
subcutaneous unfractionated heparin (10 000
IU/day) and oral aspirin (300 mg/day). Sixteen
hours later, she became comatose. The CT was
repeated and showed a massive left sided
intracranial haematoma with intraventricular
bleeding and hydrocephalus. The patient died
a few hours later.
PATHOLOGICAL EXAMINATION

Macroscopic brain examination disclosed a 6
cm diameter haematoma centred in the left
basal ganglia, with massive intraventricular
haemorrhage (fig 2 A), subarachnoid haemorrhage, and brain stem compression with
secondary right pontomesencephalic haemorrhage. There was moderate atheromathosis of
the proximal segment of the intracranial arteries. On section, the M1 segment of the left
MCA was occluded with fresh thrombotic
material, and the vessel wall was surrounded by
a blood clot which communicated with the
intracranial haematoma. No other vessels were
filled with thrombotic material. Microscopic
examination disclosed confluent zones of
necrosis in the superficial territory of the
MCA. There were fibrin deposits in the
thrombotic material. The MCA lumen was

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narrowed by an atheromatous plaque. This
atheromatous lesion was filled with blood, with
dissection of the arterial wall and extension of
the blood into the adventitial region. The diagnosis of in situ MCA dissection was established
(fig 2 B).
Discussion
There are two distinct syndromes of haemorragic transformation,1 type 1, a multifocal or
pethechial haemorrhagic infarction (haemorrhagic infarction stage c1, c2, d1, and d2
according to the classification of Moulin et al4),
and type 2, a secondary intracranial haematoma that may be identical to primary intraparenchymatous haemorrhage (intrainfarct
haematoma stage c1, c2, d1, and d2 according
to the classification of Moulin et al4). The
pathogenesis of haemorragic transformation is
multifactorial, involving reperfusion, vessel
wall damage by ischaemia, diapedesis of the
intravascular component, collateral circulation,
and other factors.1 2 Fisher and Adams suggested that the infarct is caused by blockage of
an artery by an embolus, and that subsequent
fragmentation of the embolus and relaxation of
local vascular spasm makes the embolus move
to more distal branches and exposes necrotic
tissues and damaged capillaries to reperfusion,
resulting in haemorrhage.5 Haemorragic transformation has been reported in up to 71% of
cardioembolic infarcts,6 and up to 95% of
haemorrhagic infarcts are of cardiac origin.5
Our patient had a history of hypertension and
atrial fibrillation and had undergone surgery
for mesenteric ischaemia 6 years before admission. Embolism is responsible for about 50% of
episodes of mesenteric ischaemia, and the
embolus usually originates from a left atrial or
ventricular mural thrombus.7 However, anticoagulation therapy had not been prescribed.
Pathological examination disclosed that a
transmural dissection through an atherosclerotic plaque in the proximal part of the MCA
was the direct cause of the intracranial

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de Freitas, Carruzzo, Tsiskaridze, et al

haematoma. We speculate that direct trauma in
an atheromatous vessel due to a cardiac embolus led to intima rupture. This hypothesis is
supported by one study in which arterial
rupture of the vessel wall caused by a cardiac
embolus was reported in two patients, one of
whom presented a large fatal intracranial
haematoma.8 Moreover, this assumption is
consistent with animal studies carried out in
1937 by Villaret et al, who suggested that direct
stimulation of smooth muscle cells would provoke a local and violent spasm, leading to arterial rupture.9 Anatomical studies performed by
Globus and Epstein suggested that vessel rupture is the mechanism underlying massive
intracranial haematoma; they reported that
“vessels were encountered, showing more
advanced disintegration, and often displaying a
gap through which blood apparently made its
escape into the surrounding space” and
“vessels were encountered with walls separated
(dissected) into several layers by collections of
blood.”10 We have also found other reported
cases of intracranial dissection followed by type
2 haemorragic transformation,11–13 some of
which had large intracranial haematomas and
ventricular involvement, leading to brain herniation.12 13 Given the inaccuracy of angiography in the detection of intracranial dissections14 and the lack of large pathological studies
of large haemorragic transformation (type 2),1
we propose that dissection of intracranial
arteries may underlie type 2 haemorragic
transformation in some patients. We question
whether reperfusion is essential for the development of the transformation, as pathological
examination of our patient clearly showed
occlusion of a MCA by a blood clot. Although
our assumption is not supported by experimental studies using animals, such models do
not mimic the human condition.15 Some
species present bleeding after vessel occlusion,
whereas others do not. In addition, young,
healthy animals are used for modelling stroke,
whereas human stroke often occurs in elderly

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patients with concomitant medical problems.
Both our findings and pathological8 and
experimental9 studies also suggest that trauma
caused by an embolus could lead to arterial
vessel damage and subsequent dissection.
Whether intracranial arterial dissection is an
overlooked mechanism of type 2 haemorragic
transformation still remains uncertain, and
pathological studies are still necessary. If this
proves to be the case, the implications for the
therapeutic use of anticoagulant and thrombolytic drugs in cardioembolic stroke are unknown, but might be determined by clinical
studies.
This work was supported in part by a European Neurological
Society grant to GRdeF.
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