Asymmetry of medullary veins on multiphase CT-angiography in patients with acute ischemic stroke.

BACKGROUND: It was previously demonstrated that decreased cortical venous drainage is a predictive factor of poor clinical outcome in patients with an acute ischemic stroke. The aim of this investigation is to test the hypothesis that the decline in blood flow in medullary veins (MV) on CT angiogram (CTA) of patients with acute ischemic stroke (AIS) can also be predictive of clinical outcome. METHODS: We retrospectively reviewed a database of patients with AIS who were evaluated by multiphase CTA and enrolled individuals with AIS and evidence of occlusion of the intracranial internal carotid artery, the M1 or M2 segment of the middle cerebral artery, or combination of two occlusions. To characterize asymmetry of MV we used similar principle that was previously established for MV on SWI MR-images; asymmetry was defined was presence of 5 or more contrast opacified MV in one hemisphere as compared to the contralateral side. Clinical outcomes were evaluated by mRS in 90 days. The Fisher Exact test was used to examine the significance of the MV asymmetry. Odds ratio and interrater variability were calculated. RESULTS: 66 patients with AIS were included. The presence of asymmetry in MV was associated with the higher frequency of poor clinical outcomes (84.6% vs 50.9%); the OR was 5.3. Interrater agreement in assessment on MV was moderate in our study (κ=0.55). CONCLUSION: This study shows that (a) medullary veins can be reliably assessed on multiphase CTA, (b) in patients with AIS, asymmetric appearance of MV is associated with poor clinical outcome.

Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3.

A chromosomal locus for late-onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy-confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli-Arab community. In the present study we analyzed an expanded clinical sample of 674 late-onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy-confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy-confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re-sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non-synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family-based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.