Intracerebral hemorrhage (ICH) is the most devastating type of stroke for which there are no proven effective treatments other than conservative management and supportive care.
ICH is defined as a sudden bleeding episode in the brain tissue or ventricles. It was once thought that ICH was a discrete event, but newer studies show that gradual hematoma growth is common in patients without blood clotting disorders.
Research in treatments for ICH are divided into those for primary and secondary injury. Primary injury refers to immediate effects such as increased intracranial pressure and immediate damage to the tissue from the bleeding. Secondary injury occurs after the initial hemorrhage, up to two weeks later.
There is a need for interventions to prevent the growth of the hematoma. Antifibrinolytic drugs have limited applicability because they have not shown efficacy. One study of an antifibrinolytic was stopped due to lack of efficacy, with a suggestion that either earlier treatment or higher doses were needed.
Synthetic factor VII, a therapy approved for hemophilia, has been investigated, as it is an initiator of hemostasis at sites of vascular injury. Unfortunately, it also carries a risk of deep vein thrombosis, pulmonary embolism, or myocardial infarction because it promotes blood clotting. A clinical study of factor VII showed a decrease in the onset of hematoma growth and improved clinical outcome.
Surgical evacuation of the hematoma has been studied extensively, without evidence of a clear benefit. Most neurosurgeons believe that surgical evacuation of life-threatening lobar and cerebellar hematomas is effective. Ganglionic hematomas are not considered to be good candidates for surgery.
Research goals for surgical treatment include finding new techniques such as microsurgery and endoscopy that are minimally invasive.
The role of blood pressure in secondary injury with ICH is poorly understood. It is widely believed that hypertension promotes rebleeding. However, it is also possible that attempting to treat high blood pressure will induce ischemia. More studies are needed to determine whether blood pressure management is an effective method for preventing rebleeding after ICH.
Similarly, it is unclear whether swelling in the region of the hematoma contributes to loss of neurological function, or if treatment of early edema would improve outcomes. Some studies indicate the opposite; in fact, early edema has shown a correlation with improved outcomes at 12 weeks.
There is a need for improved animal models of ICH and subsequent brain damage related to the injury. As well, the molecular and cellular mechanisms of ICH are not well understood. Basic research into those models and mechanisms can provide new ideas for treatment of ICH.
Opportunities for translational research in the area of ICH include studies of relevant proinflammatory cytokines, upstream transcription factors, immune mechanisms, and free radical therapies. Thrombin and other hemostatic proteins present in the brain after ICH could offer clues for successful treatments. As well, investigations of programmed cell death in areas surrounding a hemorrhage could yield treatments that preserve brain tissue and function.
Research in imaging is also important for ICH because of the crucial role of imaging in diagnosis, prognostic prediction, and treatment monitoring. Improved imaging techniques may be used to predict which patients could benefit the most from new therapies or surgical techniques.
Reviewed by Afsaneh Khetrapal BSc (Hons)
- Priorities for Clinical Research in Intracerebral Hemorrhage, http://stroke.ahajournals.org/content/36/3/E23.full
- Merck Manual, Professional Version, Intracerebral Hemorrhage, www.merckmanuals.com/.../intracerebral-hemorrhage
- Management of intracerebral hemorrhage, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291314/