title: Paradoxical embolism as a cause of silent brain infarctions in healthy subjects: the ICONS study (Identification of the Cause of Silent Cerebral Infarction in Healthy Subjects).
abstract: BACKGROUND
  In healthy elderly people, silent brain infarctions (SBIs) have been recognized as common lesions. In this study, we evaluated the association between SBI located outside the perforating artery territory (PAT) and paradoxical embolism detected by agitated saline transcranial Doppler (TCD) monitoring in healthy subjects.
  
  
  METHODS
  This was a prospective observational study undertaken by a university health promotion center for healthy subjects and by a university stroke center for acute stroke patients. We defined SBI as evidence on fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or more infarcts, without history of corresponding stroke or transient ischaemic attack. We also evaluated in all subjects the neuroimaging indicator of microangiopathy leukoaraiosis (LA). This study is registered with ClinicalTrials.gov, number NCT01429948.
  
  
  RESULTS
  Amongst 1103 consecutive healthy adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT, suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS was similar to cryptogenic embolic stroke (62.0%, P = 0.056), but higher than in patients with other stroke subtypes (36.2%, P = 0.021). Amongst subjects with SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01-3.14; P = 0.046).
  
  
  CONCLUSIONS
  Our results suggest that paradoxical embolism may play an important role in the development of SBI outside the PAT in apparently healthy adults.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: H Y
authors.initials: HY
authors.lastname: Shin
authors.forename: Y S
authors.initials: YS
authors.lastname: Ha
authors.forename: J W
authors.initials: JW
authors.lastname: Kim
authors.forename: K W
authors.initials: KW
authors.lastname: Kang
authors.forename: D L
authors.initials: DL
authors.lastname: Na
authors.forename: O Y
authors.initials: OY
authors.lastname: Bang
mesh_terms: D001921:Brain / Q000098:blood supply / Q000473:pathology; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D019320:Embolism, Paradoxical / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D054092:Foramen Ovale, Patent / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D049292:Leukoaraiosis / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000473:pathology; D059906:Neuroimaging / Q000379:methods; D015995:Prevalence; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D017585:Ultrasonography, Doppler, Transcranial