Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage

Harvard University, Cambridge, Massachusetts, United States
New England Journal of Medicine (Impact Factor: 55.87). 02/2000; 342(4):240-5. DOI: 10.1056/NEJM200001273420403
Source: PubMed


Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy. The factors that predispose patients to early recurrence of lobar hemorrhage are unknown. One candidate is the apolipoprotein E gene, since both the epsilon2 and the epsilon4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy.
We performed a prospective, longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage. The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and reviews of medical records and computed tomographic scans.
Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean follow-up period of 23.9+/-14.8 months, yielding a 2-year cumulative rate of recurrence of 21 percent. The apolipoprotein E genotype was significantly associated with the risk of recurrence. Carriers of the epsilon2 or epsilon4 allele had a two-year rate of recurrence of 28 percent, as compared with only 10 percent for patients with the common apolipoprotein E epsilon3/epsilon3 genotype (risk ratio, 3.8; 95 percent confidence interval, 1.2 to 11.6; P=0.01). Early recurrence occurred in eight patients, four of whom had the uncommon epsilon2/epsilon4 genotype. Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study (two-year recurrence, 61 percent; risk ratio, 6.4; 95 percent confidence interval, 2.2 to 18.5; P<0.001).
The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence. This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention.

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Available from: Heather C O'Donnell
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    • "Previous studies have established that different underlying pathologies are associated with the specific location of hemorrhage in the brain [3]. ICH located in deep brain regions (deep ICH) is a result of rupture of small arterioles most commonly in the putamen or thalamus [4] [5] [6], while ICH in lobar locations (lobar ICH), results from rupture of small and medium-sized arterial perforators in the cortex and subcortical white matter [7]. While deep perforating vasculopathy (including arteriolosclerosis, lipohyalinosis and fibrinoid necrosis, mainly driven by traditional cardiovascular risk factors) appears to underlie deep ICH [3], cerebral amyloid angiopathy (CAA), resulting from progressive cerebrovascular β-amyloid (Aβ) deposition within small cortical and leptomeningeal small vessel walls, accounts for the majority of lobar ICH in the elderly [8] [9] [10] [11]. "
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    ABSTRACT: Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia.(1).
    Full-text · Article · Dec 2015 · Biochimica et Biophysica Acta
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    • "Patients commonly present with an acute stroke syndrome with focal neurological deficits that may be associated with headache, vomiting, seizures and/or an altered level of consciousness. In the longer term, survivors of lobar ICHs are at a high risk of recurrence, especially with the presence of the ε2 or ε4 alleles of the apolipoprotein E gene (28 % cumulative recurrence rate at 2 years relative to 10 % in patients without either allele) [17]. "
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    ABSTRACT: Sporadic cerebral amyloid angiopathy (CAA) is common cause of cerebrovascular disorders that predominantly affect elderly patients. When symptomatic, cortical-subcortical intracerebral haemorrhage (ICH) in the elderly is the most well-known manifestation of CAA. Furthermore, the clinical presentation varies from a sudden neurological deficit to seizures, transient symptoms and acute progressive cognitive decline. Despite its clinical importance, this multifaceted nature poses a diagnostic challenge for radiologists. The aims of this study were to expound the characteristics of neuroimaging modalities, which cover a wide spectrum of CAA-related imaging findings, and to review the various abnormal findings for which CAA could be responsible. Radiologically, in addition to typical ICH, CAA leads to various types of abnormal findings, including microbleed, subarachnoid haemorrhage, superficial siderosis, microinfarction, reversible oedema, and irreversible leukoaraiosis. Taking into consideration the clinical importance of CAA-related disorders such as haemorrhagic risks and treatable oedema, it is necessary for radiologists to understand the wide spectrum of CAA-related imaging findings. • To describe the characteristics of imaging modalities and findings of CAA-related disorders. • MRI, especially gradient echo sequences, provides the useful information of CAA-related haemosiderin depositions. • To understand the wide spectrum of CAA-related neuroimaging and clinical features is important.
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    • "Ten to 20% of strokes are caused by ICH in Western countries.6) Over 45 years of age, ICH is common,5)16)21) but rare before then. Therefore, the goal of our study was to perform a descriptive analysis of ICH etiology and prognostic factors in patients aged ≤ 40 years. "
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    ABSTRACT: Spontaneous intracerebral hemorrhage (ICH) in young adults is rare. The purpose of this study was to investigate causes, sites and other factors affecting the prognosis of ICH in young adults aged ≤ 40 years. We reviewed 39 consecutive patients diagnosed with spontaneous ICH between January 2001 and June 2012. Patients with primary subarachnoid hemorrhage, previously diagnosed brain tumor bleeding, or vascular malformation were excluded. We analyzed the differences in prognostic factors such as hemorrhage location and vascular structural etiology. The outcome was measured using the Glasgow outcome scale (GOS), and a good outcome was defined as a score of 4 or more. We retrospectively evaluated 39 patients (mean age, 33 years; SD = 6.4, range 17 to 40 years). The most common structural etiology was arteriovenous malformation. A statistically significantly higher proportion of patients with good outcomes had a lower initial systolic blood pressure (SBP ≤ 160 mmHg, p = 0.036), a higher initial Glasgow coma scale (GCS) (9 or more, p = 0.034), lower cholesterol levels (< 200 mg/dl, p = 0.036), and smoking history (at discharge, p = 0.008; 6 months after discharge, p = 0.019). In this study, cryptogenic ICH was the leading cause of spontaneous ICH. A GCS score of 9 or more on admission, a lower serum cholesterol level (< 200 mg/dl), and a lower SBP (< 160 mmHg) predicted a good outcome.
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