We based our review on personal knowledge of the subject supplemented by data derived from multicentre randomised trials, and selected non-randomised or observational clinical studies. The information was identified with multiple searches on Medline from 2002 to the present by cross referencing the following keywords: “cerebral haemorrhage”, “intracerebral hemorrhage”, “neuroimaging”, “clinical studies”, “randomised trials”, “cytotoxicity”, “oedema”, “haemostatic treatment”, “factor VII”,
SeminarIntracerebral haemorrhage
Introduction
Non-traumatic intracerebral haemorrhage results from rupture of blood vessels in the brain. It is a major public health problem1 with an annual incidence of 10–30 per 100 000 population,1, 2 accounting for 2 million (10–15%)3 of about 15 million strokes worldwide each year.4 Hospital admissions for intracerebral haemorrhage have increased by 18% in the past 10 years,5 probably because of increases in the number of elderly people,6 many of whom lack adequate blood-pressure control, and the increasing use of anticoagulants, thrombolytics, and antiplatelet agents. Mexican Americans, Latin Americans, African Americans, Native Americans, Japanese people, and Chinese people have higher incidences than do white Americans.2, 7, 8, 9 These differences are mostly seen in the incidence of deep intracerebral haemorrhage and are most prominent in young and middle-aged people. Incidence might have decreased in some populations with improved access to medical care and blood-pressure control.8, 9, 10
Primary and secondary (anticoagulant-induced) intracerebral haemorrhage have similar underlying pathological changes.11 Intracerebral haemorrhage commonly affects cerebral lobes, the basal ganglia, the thalamus, the brainstem (predominantly the pons), and the cerebellum as a result of ruptured vessels affected by hypertension-related degenerative changes or cerebral amyloid angiopathy.1 Most bleeding in hypertension-related intracerebral haemorrhage is at or near the bifurcation of small penetrating arteries that originate from basilar arteries or the anterior, middle, or posterior cerebral arteries.12 Small artery branches of 50–700 μm in diameter often have multiple sites of rupture; some are associated with layers of platelet and fibrin aggregates. These lesions are characterised by breakage of elastic lamina, atrophy and fragmentation of smooth muscle, dissections, and granular or vesicular cellular degeneration.12, 13 Severe atherosclerosis including lipid deposition can affect elderly patients in particular. Fibrinoid necrosis of the subendothelium with subsequent focal dilatations (microaneurysms) leads to rupture in a small proportion of patients.12
Cerebral amyloid angiopathy is characterised by the deposition of amyloid-β peptide and degenerative changes (microaneurysm formation, concentric splitting, chronic inflammatory infiltrates, and fibrinoid necrosis) in the capillaries, arterioles, and small and medium sized arteries of the cerebral cortex, leptomeninges, and cerebellum.14 Cerebral amyloid angiopathy leads to sporadic intracerebral haemorrhage in elderly people, commonly associated with variations in the gene encoding apolipoprotein E, and a familial syndrome in young patients, typically associated with mutations in the gene encoding amyloid precursor protein.15 White-matter abnormalities (eg, leukoariosis) seem to increase the risk of both sporadic and familial intracerebral haemorrhage, suggesting a shared vascular pathogenesis.16, 17
Intracerebral haemorrhage associated with the taking of oral anticoagulants typically affects patients with vasculopathies related to either chronic hypertension or cerebral amyloid angiopathy, which might represent exacerbation of an existing risk of clinical and subclinical disease.16
Section snippets
Pathophysiology
The regions surrounding haematomas are characterised by oedema, apoptosis and necrosis, and inflammatory cells.18 Haematomas induce injury (figure 1) by mechanical disruption of the neurons and glia,1 followed by mechanical deformation causing oligaemia, neurotransmitter release, mitochondrial dysfunction, and membrane depolarisation.19, 20, 21 Dependent on the severity of mitochondrial dysfunction, the results of injury range from temporary metabolic suppression (hibernation phase) to cellular
Diagnosis, clinical features, and outcomes
Although CT scanning is the first-line diagnostic approach, MRI with gradient echo can detect hyperacute intracerebral haemorrhage with equal sensitivity and overall accuracy50, 51 and is more accurate for the detection of microhaemorrhages (figure 4). Perihaematomal extravasation of intravenous contrast on CT scan can detect ongoing bleeding.52, 53 Cerebral angiography is needed to diagnose secondary causes of intracerebral haemorrhage, such as aneurysms, arteriovenous malformations, dural
Overall principles
In a review of 1421 patients with intracerebral haemorrhage, care limitations or withdrawal of life-sustaining interventions was the most common (in 68%) cause of death.67 A state-wide survey in the USA68 showed that the odds of dying in hospital were associated with the frequency of use of do-not-resuscitate orders. In another study, in-hospital mortality was lower in patients treated in an intensive-care neurology unit.69 These studies provide indirect evidence that aggressive medical
Intracerebral haemorrhage related to use of oral anticoagulants
A population based study135 reported that intracerebral haemorrhage associated with oral anticoagulant use comprised 5% of all intracerebral haemorrhages in 1988, 9% in 1993–94, and 17% in 1999, with the observed increase presumably due to increasing prevalence of atrial fibrillation and higher rates of warfarin use.11 Although most cases associated with oral anticoagulant use occur when international normalised ratios are within the therapeutic range, higher ratios increase the risk.136
Future directions
Clinical evidence suggests the importance of three management tasks in intracerebral haemorrhage: stopping the bleeding,81 removing the clot,70 and controlling cerebral perfusion pressure.92 The precision needed to achieve these goals and the degree of benefit attributable to each clinical goal would be precisely defined when the results of trials in progress become available. An NIH workshop150 identified the importance of animal models of intracerebral haemorrhage and of human pathology
Search strategy and selection criteria
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