Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage

Abstract

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P <0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

Discussion on the Rehabilitation of Stroke Hemiplegia Based on Interdisciplinary Combination of Medicine and Engineering

“…The allele ε 2/ ε 4 of apolipoprotein E (APOE) is strongly associated with recurrence of OAT-ICH. Biffi et al [ 95 ] used neuroimaging to detect MRI markers of APOE ε 2/ ε 4 variants to predict OAT-ICH recurrence. Liew et al [ 96 ] also used the combination of neuroimaging and big data to establish the ENIGMA Stroke Recovery Working Group to predict the recovery of stroke patients.…”

A practical approach to the management of cerebral amyloid angiopathy

“…Apolipoprotein E alleles ∈2 (APOE2) and ∈4 (APOE4) have both been associated with CAA and risk of lobar ICH. 50–54 APOE4 is associated with increased parenchymal and vascular amyloid-β and is the strongest genetic risk factor for late onset AD, while APOE2 may track more closely with the severity of vascular pathology and ICH risk. 47,55 A recent meta-analysis demonstrated an association between cSS severity and APOE2, 56 and prior neuropathological work also identified a relationship between cSS and APOE2.…”

Neues beim Schlaganfall – Teil 1: Akuttherapie

“…Eine weitere kombinierte Analyse zweier Beobachtungsstudien (n = 230) zeigte, dass nach erlittener antikoagulationsassoziierter ICB neben lobären Mikroblu-tungen (Hazard Ratio: 1,88; 95 %-KI: 1,13 -3,12; p = 0,02) auch das Vorliegen von einer kortikalen superfiziellen Siderose (Hazard Ratio: 1,51; 95 %-KI: 1,07 -2,13; p = 0,02) und die Apolipoprotein-E-Genotypen ε2 /ε4 (Hazard Ratio: 1,90; 95 %-KI: 1,10 -3,29; p = 0,02) mit einer Rezidivblutung assoziiert waren [76]. [78,79].…”

“…blutungssensitiver MR-Sequenzen) und, falls Mikroblutungen auf eine CAA hinweisen, zu einem noch kritischeren Abwägen des möglichen Nutzens der Antikoagulation gegenüber dem deutlich erhöhten Blutungsrisiko [70,77]. Insbesondere, wenn mehr als eine lobäre Mikroblutung, eine superfizielle Siderose oder die Apolipoprotein-E-Genotypen ε2 /ε4 vorliegen [70,75,76], könnten auch alternative Strategien, wie z. B. der interventionelle Vorhofohrverschluss, in Betracht gezogen werden [77].…”