The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

December 2, 2009 —  ischemic infarction can be divided into "bland or non-hemorrhagic" infarction and infarction associated with secondary bleeding — referred to as hemorrhagic conversion or transformation (HT) — in ischemically infarcted areas. 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 hemorrhagic infarction (HI) or, less commonly, parenchymatous hemorrhage associated with a cerebral embolic infarction (PH). The occurrence of Hemorrhagic conversion is "predominantly a natural tissue consequence of embolism".

An autopsy, hemorrhagic infarction may vary from patchy petechial bleeding to more confluent hemorrhages, representing multifocal extravasation of blood from capillaries or venules. hemorrhagic infarction and PH have different incidences, pathogenesis, and clinical outcome, but distinguishing HI and PH on CT may be difficult. 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 (Fig. 1,2). 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. Fig. 3

Hemorrhagic infarction occurs regularly in the natural evolution of acute embolic stroke. Hemorrhagic transformation of an infarction can occur spontaneously in up to 30% of patients by serial CT brain scan. [1] Transformation of a bland embolic infarct to hemorrhagic infarction is rare in the first 6 hours. Most hemorrhagic infarctions are asymptomatic, and it is not uncommon to detect hemorrhagic infarction on CT patients who are stable or improving. The pathogenesis of hemorrhagic conversion or transformation in ischemically infarcted areas appears to relate to reperfusion of bleeding from recanalized but ischemically injured vessels by the natural, dynamic dissolution of thrombi 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.

Hemorrhagic infarction 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 parenchymatous hemorrhage (PH) in areas of ischemic infarction is less common that that of HI. 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 not 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".

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 [2] 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 . 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 one 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 [3]. 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 [3]. Diffuse HI associated with marked hyperglycemia has been reported in two patients [4].

In summary, HI occurs regularly in the natural evolution of acute embolic stroke and is usually asymptomatic. Parenchymatous hemorrhage associated with a cerebral embolic infarctions (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.

• Neuroimaging of hemorrhagic infarctions [5,6]

Hemorrhagic infarction is regarded as distinct from anemic infarction although microscopical haemorrhage is frequent in the later. It has frankly hemorrhagic features which consist of petechial zones that are frequently confluent and are situated in the cortex. These hemorrhagic areas may involve the entire infarction but tend most often to involve the boundary zones supplied by meningeal arterial anastomosis or, in case of middle cerebral infarct, in the basal ganglia. Hemorrhagic infarction is secondary cortical reirregation which takes place in the capillary blood vessels that have been damaged by the initial hypoxia. Reirregation takes place when lysis (natural or by therapeutic thrombolysis) or secondary mobilization of the thrombus take place.

Figure 1. Haemorrhagic infarctions. They have frankly hemorrhagic features which consist of petechial zones that are frequently confluent and are situated in the cortex. (Click to enlarge figure)

Figure 2. Noncontrast CT brain scan within 1 hour of acute onset of aphasia and right-sided weakness (A), which demonstrates an old right posterior cerebral artery territory infarct, and 24 hours later, after thrombolytic therapy (B), demonstrating dramatic hemorrhage transformation of the cerebral infarct. (Click to enlarge figure)

Figure 3. Parenchymatous hemorrhage associated with a cerebral embolic infarctions (PHs) occur less frequently, but are often symptomatic due to extension and mass effect beyond the original infarct territory. (Click to enlarge figure)

References

1. Weisberg LA. Nonseptic cardiogenic cerebral embolic stroke: clinical-CT correlations. Neurology. 1985;35(6):896–899.
2. Ogata J, Fujishima M, Tamaki K, Nakatomi Y, Ishitsuka T, Omae T (1981) Vascular changes underlying cerebral lesions in stroke-prone spontaneously hypertensive rats. A serial section study. Acta Neuropathol (Berl) 54:183–188
3. Wagner KR, Kleinholz M, de Courten-Myers GM, Myers RE.: (1992) Hyperglycemic versus normoglycemic stroke: topography of brain metabolites, intracellular pH, and infarct size. J Cereb Blood Flow Metab. 1992 Mar;12(2):213-22. [Abstract]
4. Broderick JP, Hagen T, Brott T, Tomsick T: Hyperglycemia and hemorrhagic transformation of cerebral infarcts. Stroke. 1995 Mar;26(3):484-7. [Abstract]
5. Topic of the month…..Neuroimaging of embolic brain infarction [Click to download in PDF format]
6. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 10.4a October 2009 [Click to have a look at the home page]