| 
Cerebral Embolism Formation
Hemorrhagic Conversion
 In
this example there is a gross parenchymatous hematoma with
intraventricular extension, midline shift, and herniation.
Ischemic infarction can be divided into "bland"
infarction associated with secondary bleeding -- referred
to as hemorrhagic conversion or transformation (HT) -- in
ischemically infarcted areas [Mohr JP and Sacco RL, 1992;
Teal PA and Pessin MS, 1992; Pessin MS, In: Hacke et al (eds),
1991]. Bland infarction is characterized by bland widespread
leukocyte infiltration and macrophage invasion, with only
scattered red cells being found. Hemorrhagic conversion
may take the form of infarction (HI) or, less commonly, parenchymatous
infarction (PH). The occurrence of hemorrhagic conversion
is "predominantly a natural tissue consequence of embolism"
[Teal PA and Pessin MS, 1992].
An autopsy, HI may vary from patchy
petechial bleeding to more confluent hemorrhages, representing
multifocal extravasation of blood from capillaries or venules
[Teal PA and Pessin MS, 1992]. HI and PH have different
incidences, pathogenesis, and clinical outcome, but distinguishing
HI and PH on CT may be difficult [Teal PA and Pessin MS, 1992].
Although HI and PH have often been grouped together, there
are certain features on CT that help characterize these two
types of hemorrhagic transformation. On CT, HI appears
as a discontinuous heterogeneous mixture of high and low densities
occurring within the vascular territory of the infarct.
In contrast, PH appears as a discrete, homogeneous collection
of blood that often exerts mass effect and may extend beyond
the original infarct boundaries or even into the ventricles.
 HI
occurs regularly in the natural evolution of acute embolic
stroke [Pessin MS, In: Hacke et al (eds), 1991]. In
autopsy studies, the occurrence of HI has ranged from 51%
to 71% of recent embolic strokes [Teal PA and Pessin
MS, 1992]. However, CT studies have shown a lower incidence,
with studies of con-coagulated patients who have predominantly
embolic infarcts indicating an overall incidence of 26% to
43%. According to another estimate, approximately 20%
of patients with cardioembolic stroke have hemorrhagic transformation
in the infarcted zone, usually occurring within 48 hours [Leonard
AD, Newburg S. J Neurosci Nurs. 1992;24:69]. Transformation
of a bland embolic infarct to HT is rare in the first 6 hours.
Most HIs are asymptomatic, and it is not uncommon to detect
HI on CT patients who are stable or improving. The pathogenesis
of HT appears to relate to reperfusion of bleeding from recanalized
but ischemically injured vessels by the natural, dynamic dissolution
of thrombi [Teal PA and Pessin MS, 1992] -- i.e., an embolus
that represents all or part of a thrombus has a spontaneous
tendency to lyse and disperse. Reperfusion into the
ischemically injured vessels can therefore result in varying
degrees of blood extravasation through the damaged blood-brain
barrier.
As noted by Mohr and Sacco (1992), HI has been
often explained as a result of reperfusion of the vascular
bed of the infarct, such as would occur after fragmentation
and distal migration of an embolus or after early reopening
of a large vessel occlusion in the setting of a large infarction;
the full pressure of arterial blood into hypoxic capillaries
results in a diapedesis or red cells through their hypoxic
walls. The concept of restored lumen patency is consistent
with greater frequency of hemorrhagic infarction in patients
with cardioembolic infarcts.
 The
occurrence of PH in areas of ischemic infarction is
less common that that of HI [Teal PA and Pessin MS, 1992].
PH appears to be associated with anticoagulation therapy,
with a low incidence of spontaneous PH in areas of ischemic
infarction (on the order of 2% to 9%) in patients no receiving
anticoagulation therapy. In contrast to HI, clinical
deterioration is often associated with PH. It has been
proposed that the pathogenesis of PH may involve "ischemic
necrosis resulting in the rupture of small penetrating vessels
analogous to hypertensive hemorrhage, leading to massive bleeding
rather that the multifocal diapedesis of blood through capillary
walls, as seen in HI" [Teal PA and Pessin MS, 1992].
The observation that some hemorrhagic infarctions
develop distal to the site of a persisting occlusion suggests
that reperfusion is not always a necessary condition.
Investigators from Japan examined the brains of 14 patients
who died from herniation of the brain after cardioembolic
stroke with persistent occlusion of the internal carotid-middle
arterial axis [Ogata J, et al. Stroke. 1989;20:876-83].
The finding of hemorrhagic infarct in 7 of the patients contradicts
the concept that reopening a previously occluded vessel is
the only pathophysiologic mechanism for the development of
hemorrhagic infarct. Analysis of blood pressure after
stroke has revealed on or more surges of arterial hypertension
or rapid rise of blood pressure in patients with hemorrhagic
stroke without a reopening of the occluded artery; it has
been speculated that these blood pressure rises might explain
hemorrhagic infarction in many cases.
A relationship between hyperglycemia and hemorrhagic
transformation has also been suggested by he observation that
occluding the middle cerebral artery of markedly hyperglycemia
cats was associated with 5-fold more frequent and 25-fold
more extensive hemorrhage into infarcts than in normoglycemic
animals [de Courten-Myers GM, et al. 1992]. Compared
with permanent occlusion, temporary restoration of blood flow
after 4 hours caused the most extensive hemorrhage into infarcts.
It was concluded that hyperglycemia and restoration of blood
flow to ischemic territories were strong risk factors for
hemorrhagic infarct conversion. The evidence suggests
that the marked tissue energy depletion accompanied by acidosis
damages brain vessels, causing leakage of edema fluid and
red blood cells [de Courten-Myers GM, et al, 1992].
Diffuse HI associated with marked hyperglycemia has been reported
in two patients [Broderick JP, et al, 1995].
In summary, HI occurs regularly in the natural
evolution of acute embolic stroke and is usually asymptomatic
[Pessin MS, In: Hacke et al (eds), 1991]. PHs occur
less frequently, but are often symptomatic due to extension
and mass effect beyond the original infarct territory.
Interest in these issues has been further generated by trials
of thrombolytic therapy for acute ischemic stroke.
|
Stroke Education
