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.[6][7] Stroke is the second largest cause of death globally (5.5 million deaths) after ischaemic heart disease.[8] Haemorrhagic stroke accounts for about 10% of strokes, but is responsible for more deaths and disability-adjusted life-years lost than ischaemic stroke.[9] Three-quarters of haemorrhagic strokes are intracerebral haemorrhage, and the remainder are subarachnoid haemorrhage.[9]
The global prevalence of intracerebral haemorrhage (ICH) was 18.88 million cases in 2020.[10] There was a decrease of 3.33% in the age-standardised prevalence rate from 2010 to 2020.[10] Globally, the number of deaths attributable to ICH in 2020 was 3.25 million.[9] The age-standardised mortality rate decreased between 2010 and 2020.[9][10]
The incidence of ICH rises with age and is increased in certain groups.[11] Overall, men have a higher incidence compared with women, although the difference lessens with age.[9] Black people and people of Asian or Latino/Hispanic origin have a higher rate of ICH than white people.[9][12][13]
Risk factors
Associated with increased incidence of ICH although the difference lessens with age.[9]
Associated with increased incidence of ICH.[9][25] Some, but not all, of this increased risk is accounted for by higher prevalence of hypertension.[26][27]
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.[28]
Associated with an increased risk of ICH.[24]
Drugs, such as cocaine and amphetamine, have been associated with intracerebral haemorrhage.[24]
Epidemiological studies show that a significant portion of sporadic ICH risk is heritable, and that family history of ICH is a risk factor.[29]
Hereditary bleeding disorders, including haemophilia, may be complicated by ICH.
Sporadic cerebral amyloid angiopathy (CAA), a common age-related cerebral small vessel disease, is an important cause of lobar ICH, particularly in older people.[30] The risk of recurrent ICH in patients with CAA is approximately 7% per year compared to about 1% for ICH associated with arteriolosclerosis.[30][31] 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.[16]
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.[14][32][33][34]
The incidence rate of haemorrhagic stroke in patients with sickle cell anaemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common aetiologies for haemorrhage.[35]
Rare autosomal dominant mutations in the COL4A1 gene cause intracerebral haemorrhage, retinal haemorrhages, and porencephaly (cyst or cavity in the cerebral hemispheres).[36]
Caused by mutations in the ACVRL1, ENG, or SMAD4 gene. High prevalence of brain arteriovenous malformations, which in turn increases the risk of ICH.[19]
May lead to cavernous malformations.
These include arteriovenous malformations, dural arteriovenous fistulas, and cavernous malformations.[39]
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.[40] Patients with this vasculopathy also have an increased risk for cerebral aneurysms.
The risk of non-traumatic ICH is increased during pregnancy and the postnatal period. One retrospective review showed 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the same age range).[41] The increased risk of ICH associated with pregnancy is largely attributable to ICH occurring in the postnatal period.[41][42] Peripartum angiopathy, eclampsia, HELLP syndrome, and sinus venous thrombosis can cause ICH in pregnant women.[23] Pre-existing risk factors associated with ICH include increasing maternal age, non-white race, and chronic hypertension.[42]
The association with ICH is unclear, with only a few studies documenting risk.[43]
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.[44]
Severe obstructive sleep apnoea doubles the risk for incident stroke, especially in young to middle-aged people. Continuous positive airway pressure (CPAP) may reduce stroke risk, but trials have not provided a high level of evidence to support the benefits of CPAP for primary stroke prevention.[45][46]
A case-control study showed a relationship between the over-the-counter drug phenylpropanolamine, now discontinued from the market, and ICH.[50] 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.[51]
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.[52]
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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