Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis

Poon, Michael T C; Fonville, Arthur F.; Salman, Rustam Al-Shahi

doi:10.1136/jnnp-2013-306476

Cited by 496 publications

(432 citation statements)

References 54 publications

(95 reference statements)

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“…2 Previous studies demonstrated that survivors of ICH in the lobar brain regions are at higher risk of recurrence, and multiple predictors of recurrent lobar ICH have been identified. 3,4 Among these, the e2/e4 variants of the APOE gene are presumed to modify lobar ICH recurrence risk via their role in small vessel disease associated with cerebral amyloid angiopathy (CAA).…”

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confidence: 99%

APOE ε4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage

et al. 2015

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Objective: Genetic variants e2/e4 within the APOE gene are established risk factors for lobar intracerebral hemorrhage (ICH). Published preliminary data suggest a potential role for APOE e4 in risk of nonlobar ICH. We therefore investigated the role of APOE in recurrent nonlobar ICH, and sought to clarify whether effects of APOE on circulating lipids mediate this association.Methods: Three hundred sixty-three survivors of nonlobar ICH were followed prospectively for ICH recurrence, with APOE genotype determined at enrollment. All participants had clinical, demographic, and laboratory data captured at time of index ICH and during follow-up. Using a multivariate model, we performed association and interaction analyses of the relationships among APOE genotype, lipid levels, and recurrent nonlobar ICH. Results:We observed 29 nonlobar ICH recurrences among 363 survivors. APOE e4 was associated with recurrent nonlobar ICH (hazard ratio 5 1.31; 95% confidence interval 5 1.02-2.69; p 5 0.038) after adjustment for age/sex/ethnicity and cardiovascular risk factors. Increasing lowdensity lipoprotein (LDL) levels were associated with decreased risk of recurrent nonlobar ICH (p 5 0.027), as were decreasing HDL levels (p 5 0.046). LDL levels modified the association of APOE e4 with recurrent nonlobar ICH (mediation p , 0.05). No associations were identified between APOE e2 and recurrent nonlobar ICH.Conclusion: APOE e4 is associated with recurrent ICH in nonlobar brain regions, providing further evidence for its causal role in ICH unrelated to cerebral amyloid angiopathy. LDL levels modulated this effect, suggesting that circulating lipid levels may mediate a portion of the role of APOE e4 in nonlobar ICH. Neurology ® 2015;85:349-356 GLOSSARY CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; EMR 5 electronic medical record; HDL 5 high-density lipoprotein; HR 5 hazard ratio; ICH 5 intracerebral hemorrhage; IQR 5 interquartile range; LDL 5 low-density lipoprotein; TC 5 total cholesterol.Primary intracerebral hemorrhage (ICH) is the most lethal acute cerebrovascular disorder, its mortality rate ranging from 40% to 50% at 90 days from the initial bleeding event.1 Survivors are often burdened with substantial disability and face a high risk of recurrent ICH.2 Previous studies demonstrated that survivors of ICH in the lobar brain regions are at higher risk of recurrence, and multiple predictors of recurrent lobar ICH have been identified.3,4 Among these, the e2/e4 variants of the APOE gene are presumed to modify lobar ICH recurrence risk via their role in small vessel disease associated with cerebral amyloid angiopathy (CAA). 3,5 A recent, large meta-analysis of case-control studies conclusively demonstrated that APOE e2 and e4 increase risk of ICH in the lobar brain regions. 6 An intriguing preliminary finding that emerged as well was an association between APOE e4, but not e2, and nonlobar ICH.6 This finding warrants further exploration of its potential underlying biology, as nonlobar ICH is typically associate...

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APOE ε4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage

et al. 2015

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“…Secondary brain injuries may lead to delayed fatality when death does not occur shortly after the onset. One-year and five-year survival are estimated to be around merely 46% and 29%, respectively [10] . Beyond that, surviving patients are usually left with many limitations in motor and cognitive functions.…”

Section: Epidemiologymentioning

confidence: 99%

Stem cell therapy in intracerebral hemorrhage rat model

Cordeiro

Horn

2015

WJSC

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Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. Core tip: In this review, we first summarize intracerebral hemorrhage (ICH) epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts.Cordeiro MF, Horn AP. Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells 2015; 7(3): 618-629

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“…Subsequently, the annual risk of recurrent sICH is estimated to be 2-3%. 41 However, certain factors are associated with higher risk of recurrent sICH, including poorly controlled hypertension (three-to fourfold risk), 42 cerebral amyloid angiopathy (Fig 2 , up to 22% per year), 43 lobar haemorrhage (3-14% per year), 44 arteriovenous malformation (18% per year) and cerebral microbleeds on MRI (eightfold risk). 45 The risk of recurrent sICH increases three-to fivefold in patients taking VKA.…”

Section: Risk Of Recurrent Ichmentioning

confidence: 99%

Management of acute intracerebral haemorrhage – an update

et al. 2017

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Managing acute intracerebral haemorrhage is a challenging task for physicians. Evidence shows that outcome can be improved with admission to an acute stroke unit and active care, including urgent reversal of anticoagulant effects and, potentially, intensive blood pressure reduction. Nevertheless, many management issues remain controversial, including the use of haemostatic therapy, selection of patients for neurosurgery and neurocritical care, the extent of investigations for underlying causes and the benefi t versus risk of restarting antithrombotic therapy after an episode of intracerebral haemorrhage.

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Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis

Abstract: Less than a half of patients with ICH survive 1 year and less than a third survive 5 years. Risks of recurrent ICH and ischaemic stroke after ICH appear similar after ICH, provoking uncertainties about the use of antithrombotic drugs.

Cited by 496 publications

References 54 publications

APOE ε4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage

APOE ε4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage

Stem cell therapy in intracerebral hemorrhage rat model

Management of acute intracerebral haemorrhage – an update

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