title: Apolipoprotein E genotype is associated with CT angiography spot sign in lobar intracerebral hemorrhage.
abstract: OBJECTIVE
  The CT angiography (CTA) spot sign predicts hematoma expansion and poor outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood; it may be that the underlying vasculopathy influences its presence. Therefore, we conducted a study to identify genetic predictors of the spot sign.
  
  
  METHODS
  In an ongoing prospective cohort study, we analyzed 371 patients with CTA and genetic data available. CTAs were reviewed for the spot sign by 2 experienced readers, blinded to clinical data, according to validated criteria. Analyses were stratified by ICH location.
  
  
  RESULTS
  In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location (OR, 3.85; 95% CI, 1.33-11.13 in deep ICH and OR, 2.86; 95% CI, 1.33-6.13 in lobar ICH). Apolipoprotein E ε2, but not ε4, was associated with the presence of a spot sign in lobar ICH (OR, 2.09; 95% CI, 1.05-4.19). There was no effect for ε2 or ε4 in deep ICH.
  
  
  CONCLUSIONS
  Patients with ICH on warfarin are more likely to present with a spot sign regardless of ICH location. Among patients with lobar ICH, those who possess the apolipoprotein E ε2 allele are more likely to have a spot sign. Given the established relationship between apolipoprotein E ε2 and vasculopathic changes in cerebral amyloid angiopathy, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence.
authors.affiliation: Center for Human Genetic Research-Rosand Lab, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. brouwers@chgr.mgh.harvard.edu
authors.forename: H Bart
authors.initials: HB
authors.lastname: Brouwers
authors.forename: Alessandro
authors.initials: A
authors.lastname: Biffi
authors.forename: Kristen A
authors.initials: KA
authors.lastname: McNamara
authors.forename: Alison M
authors.initials: AM
authors.lastname: Ayres
authors.forename: Valerie
authors.initials: V
authors.lastname: Valant
authors.forename: Kristin
authors.initials: K
authors.lastname: Schwab
authors.forename: Javier M
authors.initials: JM
authors.lastname: Romero
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Goldstein
mesh_terms: D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D053329:Apolipoprotein E2 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015600:Glasgow Coma Scale; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D014859:Warfarin; D004247:DNA