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Neurology. 2014 Nov 11;83(20):1838-43. doi: 10.1212/WNL.0000000000000984. Epub 2014 Oct 15.

Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy.

Author information

1
From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
2
From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA. sgreenberg@mgh.harvard.edu.

Abstract

OBJECTIVE:

We sought to explore the mechanisms leading to cerebral amyloid angiopathy (CAA)-related cortical superficial siderosis (cSS) by examining its neuroimaging and genetic association with cerebral microbleeds (CMBs).

METHODS:

MRI scans of 84 subjects with probable or definite CAA participating in a longitudinal research study were graded for cSS presence and severity (focal, restricted to ≤ 3 sulci vs disseminated, ≥ 4 sulci), and CMB count. APOE ε variants were directly genotyped. We performed cross-sectional analysis comparing CMB counts and APOE ε2 and ε4 allele frequency between subjects with no, focal, or disseminated cSS.

RESULTS:

cSS was present in 48% (n = 40) of the population. APOE ε2 was overrepresented among participants with focal (odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-29.3, p = 0.008) and disseminated (OR 11.5, 95% CI 2.8-46.2, p = 0.001) cSS relative to individuals without cSS. CMB counts decreased with increasing severity of cSS (median: 41, 38, and 15 for no cSS, focal cSS, and disseminated cSS, respectively, p = 0.09). The highest CMB count tertile was associated with APOE ε4 (OR 3.0, 95% CI 1.4-6.6, p = 0.006) relative to the lowest tertile.

CONCLUSIONS:

Among individuals with advanced CAA, cSS tends to occur in individuals with relatively lower CMB counts and with a distinct pattern of APOE genotypes. These results suggest that CAA-related cSS and CMBs may arise from distinct vasculopathic mechanisms.

PMID:
25320098
PMCID:
PMC4240429
DOI:
10.1212/WNL.0000000000000984
[Indexed for MEDLINE]
Free PMC Article

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