Epidemiology

There are more than 100,000 strokes in the UK each year causing 38,000 deaths, making it a leading cause of death and disability.[4][5][6] People are most likely to have a stroke over the age of 55.[7][6] Stroke is the second largest cause of death globally (5.5 million deaths) after ischaemic heart disease.[8]

In 2017, the global prevalence of stroke was 104.2 million people; that of ischaemic stroke was 82.4 million people and intracerebral haemorrhage (ICH) 17.9 million people.[9]

The incidence of ICH rises with age and is increased in certain groups. Overall, men have a higher incidence compared with women. Moreover, Asian people have a higher rate of ICH compared with other ethnic groups, including black people and people of Hispanic ethnicity.[10][11]

Risk factors

Uncontrolled hypertension is the most common risk factor for spontaneous intracerebral haemorrhage (ICH).[22]

Associated with increased incidence of ICH.[22]

Associated with increased incidence of ICH.[10]

Associated with increased incidence of ICH.[10][23] Some, but not all, of this increased risk is accounted for by higher prevalence of hypertension.[24][25]

There is a two times higher rate of ICH in Asian people compared with other ethnic groups. Japanese men had a higher incidence than Japanese women. This suggests a difference in cardiovascular risk factors as well as influence from environmental factors.[11]

Associated with an increased risk of ICH.[22]

Illegal drugs, particularly sympathomimetic drugs, such as cocaine and amphetamine, have been associated with intracerebral haemorrhage.[22]

Epidemiological studies show that a significant portion of sporadic ICH risk is heritable, and that family history of ICH is a risk factor.[26]

Hereditary bleeding disorders, including haemophilia, may be complicated by ICH.

Most cases of cerebral amyloid angiopathy are non-familial. Cerebral amyloid angiopathy can rarely be caused by autosomal dominant mutations involving the amyloid precursor protein, cystatin-C, or transthyretin genes.[14]

Additional non-modifiable risk factors for recurrent primary lobar haemorrhage have been identified in those with presumed cerebral amyloid angiopathy: number of MRI microbleeds, presence of white matter lesions on CT, and the presence of one or more apolipoprotein E epsilon 2 or epsilon 4 alleles.[12][27][28][29]

Rare autosomal dominant mutations in the COL4A1 gene cause intracerebral haemorrhage, retinal haemorrhages, and porencephaly (cyst or cavity in the cerebral hemispheres).[30]

Caused by mutations in the ACVRL1, ENG, or SMAD4 gene. High prevalence of brain arteriovenous malformations, which in turn increases the risk of ICH.[17]

May lead to cavernous malformations.

Clinical trials show that aspirin confers a very small increased risk, with warfarin conferring a more substantial risk.[31][32]

These include arteriovenous malformations, dural arteriovenous fistulas, and cavernous malformations.[33]

The risk of bleeding depends on the type of malformation, pattern of venous drainage, and history of previous bleeds.

Moyamoya syndrome and Moyamoya disease are associated with parenchymal and intraventricular haemorrhage, predominantly in paediatric patients. The re-bleeding rate is approximately 7% per year.[34] Patients with this vasculopathy also have an increased risk for cerebral aneurysms.

The association with ICH is unclear, with only a few studies documenting risk.[35]

As a single group, NSAIDs did not have significant correlation with higher incidence of ICH, although among users of specific agents (diclofenac and meloxicam) a significant increased risk was observed.[36]

Not a well-recognised risk factor despite some study findings.[35]

A case-control study showed a relationship between the over-the-counter drug phenylpropanolamine, now discontinued from the market, and ICH.[37] There is no consistent evidence that other sympathomimetic drugs, including cold remedies, are associated.

Use of higher doses of the herbal medicine ephedra has been linked with haemorrhage risk in a case-control study.[38]

Although a relatively infrequent cause of intracerebral or subarachnoid haemorrhage, cerebral vasculitis should be considered in a setting of relevant systemic symptoms, an unexplained progressive neurological disorder, or in a patient lacking risk factors for haemorrhagic stroke. Diagnosis is achieved after a high level of suspicion with conventional angiography and leptomeningeal biopsy.[39]

Platelet counts less than 20,000/microlitre are associated with spontaneous ICH. Factors such as uraemia and heavy alcohol use are well known to cause dysfunctional platelet aggregation (thrombocytopathy) and act as the main mechanism for bleeding.

Leukaemia is associated with parenchymal haemorrhage and cerebral venous thrombosis independently of thrombocytopenia.

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