Explorer European research priorities for intracerebral haemorrhage

Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions reReceived: March 31, 2011 Accepted: July 1, 2011 Published online: October 8, 2011 Thorsten Steiner Department of Neurology Heidelberg University Hospital, Im Neuenheimer Feld 400 DE–69120 Heidelberg (Germany) Tel. +49 6221 56 38673, E-Mail thorsten-steiner @ med.uni-heidelberg.de © 2011 S. Karger AG, Basel 1015–9770/11/0325–0409$38.00/0 Accessible online at: www.karger.com/ced Steiner et al. Cerebrovasc Dis 2011;32:409–419 410 ICH can be differentiated into arterial small and large vessel disease, venous disease, vascular malformation, haemostatic disorders, ICH in the context of other diseases and conditions, and spontaneous. ‘Spontaneous’ means that no cause has been found with the currently available diagnostic tests, though it is assumed that there is a cause (cryptogenic). Spontaneous also includes that no cause has been found so far, and there is no suspicion about a concept for a cause (idiopathic). A proposal for a detailed ICH classification by causes is currently prepared in the frame of the new ICH guidelines from the European Stroke Organisation. Spontaneous ICH, which is apparently unrelated to trauma, has incurred unchanged global burden over the past decades [2, 3] . In contrast to the declining incidence of ischaemic stroke in high-income countries [4] , the incidence of ICH has been constant [3] . Worldwide, the World Health Organisation estimates that 15.3 million strokes occur every year [5] , of which 2–3 million are haemorrhagic. The cost of stroke in the European Union has been estimated at 27 billion EUR, of which 8.5 billion EUR are indirect costs [6] . The additional cost of ICH is estimated to be 30,000–45,000 EUR/survivor every year [7] . During the last decade, spontaneous ICH accounted for approximately 10% of strokes in high-income countries and about 20% of strokes in low-/middle-income countries, with 1-month case fatalities of 25–35 and 30– 48%, respectively [4] . Cerebrovascular disease mortality also varies widely in Europe [8] . Unfortunately, the 1-month case fatality after ICH does not appear to have changed over the last few decades [3] . This is in contrast to the recent decline in the case fatality after subarachnoid haemorrhage [9, 10] , which may be explained by multiple factors [11] , including advances in endovascular treatment of intracranial aneurysms and intensive care after intervention [9, 12] . The incidence of spontaneous ICH is higher in Asians [3] , and the major risk factors for ICH include male gender, increasing age, arterial hypertension, excessive alcohol consumption, smoking, diabetes mellitus, poor diet and obesity (waist-to-hip ratio) [13, 14] . However, over the past decades, the incidence of ICH associated with prestroke hypertension appears to have declined, whereas ICH associated with use of antithrombotic drugs and presumed cerebral amyloid angiopathy in those aged 6 75 years seems to have increased [2] . Impact for Research As life expectancy rises, so will the burden of ICH. We need a better understanding of the roles of various risk factors for ICH in the elderly, to what extent they are causal and modifiable, and whether demographic transitions in low-income countries and low social status result in a larger proportion of deaths being due to ICH. We need more information on ICH epidemiology in lowand middle-income countries to compare racial, ethnic and population differences, as well as more estimates of ICH case fatality rates during different epochs in order to understand why they appear to have declined in some regions but not in others [3] . A joint prospective multinational study on the incidence, prevalence and socio-economic impact of spontaneous ICH – ideally – in all European Union countries is needed to propose more specific actions to be taken by health authorities at European and national levels. Pathophysiology of ICH and Impact of Brain Banking Most data on the pathophysiology of human ICH come from early macroscopic autopsy studies and describe neural damage from the hydrostatic pressure of ICH. Most instances of ICH occur when small (50to 700m) penetrating arteries rupture with subsequent leaking of arterial blood into the brain parenchyma. The mass effect of the haematoma destroys neighbouring brain structures and compresses remote brain regions by midline shift and herniation. Rebleeding or haematoma growth and intraventricular expansion complicate the ICH in up to 70% of all patients within 24 h [15] . The fixed shape of the cranium limits its capacity to accommodate the volumetric ICH expansion, and haematoma volumes over 150 ml almost inevitably lead to death. The intact or partially intact brain tissue around the haematoma may resemble ischaemic brain, and neurons may die by similar mechanisms or may be subject to toxic effects of blood products. However, studies have been contradictory about the presence, extent and severity of any penumbra around ICH. Blood-brain barrier disruption and leakage of fluids and proteins contribute to brain oedema, which commonly increases over several days and may further damage the brain [16] . At a later stage, erythrocyte lysis and release of haemoglobin metabolites, iron and thrombin have been shown to trigger neurotoxic and apoptotic mechanisms in animals [17, 18] . Another potential pathogenetic mechanism is activation of leucocytes at the injury site within the first few days, attributable to the widespread inflammation seen in animal models of ICH. All injuries to brain tissue also change genomic expression in the brain [19] , which is a largely