Treatment and Prevention of Primary Intracerebral Hemorrhage

Abstract

Intracerebral hemorrhage (ICH), which constitutes 10 to 15% of all strokes and affects approximately 65,000 people each year in the United States, has the highest mortality rate of all stroke subtypes. Hypertension, cerebral amyloid angiopathy, and anticoagulation underlie the majority of cases of ICH. Warfarin not only increases the risk but also increases the severity of ICH by causing hematoma expansion. With the advent of gradient-echo magnetic resonance imaging, patients with underlying cerebral amyloid angiopathy or hypertensive vasculopathy can be identified, and measures can be taken to prevent ICH. Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies. Although a treatment for cerebral amyloid angiopathy does not exist, agents targeting beta-amyloid metabolism and bioactivity are promising candidates. Strategies for preventing warfarin-associated hemorrhage include strict monitoring of anticoagulation levels and using agents such as direct thrombin inhibitors. The future of ICH management lies in therapies targeted at the pathophysiological steps in ICH. Potential treatments include glutamate receptor antagonists for preventing glutamate excitotoxicity, matrix metalloproteinase and thrombin inhibitors for preventing perihematomal edema, and recombinant activated factor VII for preventing hematomal expansion.

Magnetic Resonance Imaging Detection and Time Course of Cerebral Microhemorrhages during Passive Immunotherapy in Living Amyloid Precursor Protein Transgenic Mice

“…T2*-weighted MR microscopy can be readily applied to screening all A␤-targeted immunotherapeutics in a longitudinal manner. This methodology can also be used in the evaluation of compounds directly targeting CAA, which is a disorder of growing societal importance and with few therapeutic options (Towfighi et al, 2005). Therefore, the information generated using this technology has the potential to directly translate to human clinical trials and thus may accelerate drug innovation.…”

Warfarin Reversal in Anticoagulant-Associated Intracerebral Hemorrhage

“…The majority of survivors suffer long-term neurologic deficits and are unable to return to independent levels of function [1]. While hematoma formation causes injury by multiple mechanisms [5][6][7][8], the most significant factor influencing outcome is mass effect from the hematoma itself [9,10]. Therefore, interventions that minimize ongoing bleeding are likely to be critical for improving outcomes.…”

Active and Passive Immunotherapy for Neurodegenerative Disorders

“…This finding raises a new safety concern that may be relevant to humans because ∼90% of human AD patients have concomitant CAA, and similar intracranial hemorrhages were seen in one actively vaccinated patient (Ferrer et al 2004). Most of these hemorrhages were small, and the clinical significance of these microbleeds is not entirely certain; they can be found frequently in asymptomatic patients with CAA (Towfighi et al 2005). Likewise, one preclinical passive vaccination study reported that although there were larger numbers of microhemorrhages and worsening CAA in antibody-treated mice, these did not negate the generally positive effects of treatment on behavioral performance (Wilcock et al 2004b).…”