The Persisting Burden of Intracerebral Haemorrhage: Can Effective Treatments Be Found?

Spontaneous intracerebral haemorrhage (ICH) that is apparently unrelated to trauma or an underlying vascular, neoplastic, or coagulopathic cause has incurred the same global burden over the past quarter of a century [1,2]. During the last decade, spontaneous ICH accounted for ,10% of strokes in high income countries and ,20% of strokes in low and middle income countries, where the one month case fatalities were 25%–35% and 30%–48%, respectively [3]. The incidence of ICH is higher in Asians [2], and the major risk factors for spontaneous ICH without an identified cause (socalled primary ICH) are male gender, systemic arterial hypertension, excessive alcohol consumption, increasing age, smoking, and diabetes mellitus [4]. However, over the past quarter of a century, the incidence of primary ICH associated with pre-stroke hypertension seems to have declined, whereas there seems to have been an increase associated with antithrombotic use and presumed cerebral amyloid angiopathy in those aged $75 years [1]. Whilst primary prevention with antihypertensive medication is probably the most effective strategy to reduce the burden of ICH, could the management of ICH influence outcome? The outcome after primary ICH seems to be worse than after a bleed secondary to an arteriovenous malformation [5], which justifies thorough investigation for all patients (Table 1). However, there is a shortage of evidence and lack of consensus about who, when, and how to further investigate for a cause underlying ICH [6]. There appears to be a modest association between ICH deep in the brain and hypertension, and between ICH in the lobes of the brain and cerebral amyloid angiopathy [7,8], but these associations by no means rule out the need for further investigation of patients who are likely to survive and benefit from the identification of a treatable underlying cause (Table 1) [9]. Apart from identifying and treating underlying causes of ICH, this review focuses on other strategies to improve outcome, bearing in mind the pathophysiological mechanisms underlying clinical deterioration after ICH. We go on to address the treatments for primary ICH that are supported by randomised controlled trials (RCTs) and those that are not, and discuss which interventions appear to be the most promising in ongoing and future RCTs.