Spontaneous intracerebral hemorrhage (SICH) accounts for approximately 13-17% of all stroke; however, carries a substantial mortality; approaching approximately 50% within 3-months and severe disability in the majority of survivors. Half of these deaths occur within the acute phase of intracerebral hemorrhage (ICH). Volume of hemorrhage, secondary expansion, and clinical examinations are some of the determinant of mortality and morbidity. The pathophysiology behind early hematoma expansion remains poorly understood. It remains unclear whether hematoma expansion reflects additional leakage, rebleeding or both. To date; not a single pathway has been directly linked to injury; but rather several pathways are thought to act in synergy; ultimately leading to further cerebral injury. The concept of “peri-hemorrhagic penumbra” has also been put forth in animal models; and numerous studies have demonstrated decreased cerebral blood flow in the area surrounding the primary hematoma, which may lead to further cytotoxic edema and toxic release of inflammatory and cytotoxic mediators. Early animal models have suggested the concept of “peri-hemorrhagic ischemia” surrounding the primary hematoma, and in some cases, infarction around the hematoma. These early models and experiments led to the widely accepted concept of acute blood pressure control in such patients. However, subsequent metabolism and flow-studies demonstrated that such peri-hematoma changes were far from universal. Additional evidence came forth supporting the role for inflammation as an important component in the process of peri-hematoma edema formation, particularly neutrophils activation, free-radical formation and expression of interleukin-6 (IL-6) and tumor-necrosis alpha (TNF-a). Albeit the thought for the role of disturbed autoregulation and uncontrolled perfusion pressure in hypertension as a driving force is conceivable; this remains under much debate as the leading role of hematoma expansion. If one could predict the chance of hematoma expansion and peri-hemorrhagic edema at baseline; such could constitute the first step toward an effective therapy. Albeit numerous trials investigated various potential predictor of H.E yet inconsistent evidence have been produced. In theory; if one could stop the bleeding during the acute phase of SICH or remove the accumulated blood without additional brain parenchyma disruption; one could theoretically prevent further neurological deterioration or poor outcome in SICH. Unfortunately almost all of the “classical” approaches have failed to shown a significant impact on HE in regard of outcome in randomized clinical trials. This is probably related to both disease inherent but also trial inherent reasons. Current treatment strategies may remain “double-edged swords”; for inherent reasons to the pathophysiology of SICH. Therefore the right balance and possibly the combination of current accepted strategies as well as the evaluation of future approaches seem urgent. This topic will continue to evolve as our understanding of the pathogenesis of SICH and secondary HE continue to evolve.
In this research topic, the author will discuss the controversies that surround our understanding of direct and indirect mechanisms of secondary brain injury following spontaneous intracerebral hemorrhage. This topic will include review the role of disturbed autoregulation following sICH, surgical and non-surgical approaches in management of sICH, peri-hematoma edema, peri-hematoma expansion, and future therapeutic trends.
Spontaneous intracerebral hemorrhage (SICH) accounts for approximately 13-17% of all stroke; however, carries a substantial mortality; approaching approximately 50% within 3-months and severe disability in the majority of survivors. Half of these deaths occur within the acute phase of intracerebral hemorrhage (ICH). Volume of hemorrhage, secondary expansion, and clinical examinations are some of the determinant of mortality and morbidity. The pathophysiology behind early hematoma expansion remains poorly understood. It remains unclear whether hematoma expansion reflects additional leakage, rebleeding or both. To date; not a single pathway has been directly linked to injury; but rather several pathways are thought to act in synergy; ultimately leading to further cerebral injury. The concept of “peri-hemorrhagic penumbra” has also been put forth in animal models; and numerous studies have demonstrated decreased cerebral blood flow in the area surrounding the primary hematoma, which may lead to further cytotoxic edema and toxic release of inflammatory and cytotoxic mediators. Early animal models have suggested the concept of “peri-hemorrhagic ischemia” surrounding the primary hematoma, and in some cases, infarction around the hematoma. These early models and experiments led to the widely accepted concept of acute blood pressure control in such patients. However, subsequent metabolism and flow-studies demonstrated that such peri-hematoma changes were far from universal. Additional evidence came forth supporting the role for inflammation as an important component in the process of peri-hematoma edema formation, particularly neutrophils activation, free-radical formation and expression of interleukin-6 (IL-6) and tumor-necrosis alpha (TNF-a). Albeit the thought for the role of disturbed autoregulation and uncontrolled perfusion pressure in hypertension as a driving force is conceivable; this remains under much debate as the leading role of hematoma expansion. If one could predict the chance of hematoma expansion and peri-hemorrhagic edema at baseline; such could constitute the first step toward an effective therapy. Albeit numerous trials investigated various potential predictor of H.E yet inconsistent evidence have been produced. In theory; if one could stop the bleeding during the acute phase of SICH or remove the accumulated blood without additional brain parenchyma disruption; one could theoretically prevent further neurological deterioration or poor outcome in SICH. Unfortunately almost all of the “classical” approaches have failed to shown a significant impact on HE in regard of outcome in randomized clinical trials. This is probably related to both disease inherent but also trial inherent reasons. Current treatment strategies may remain “double-edged swords”; for inherent reasons to the pathophysiology of SICH. Therefore the right balance and possibly the combination of current accepted strategies as well as the evaluation of future approaches seem urgent. This topic will continue to evolve as our understanding of the pathogenesis of SICH and secondary HE continue to evolve.
In this research topic, the author will discuss the controversies that surround our understanding of direct and indirect mechanisms of secondary brain injury following spontaneous intracerebral hemorrhage. This topic will include review the role of disturbed autoregulation following sICH, surgical and non-surgical approaches in management of sICH, peri-hematoma edema, peri-hematoma expansion, and future therapeutic trends.
