No abstract

Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between “northern” and “southern” European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the “southern” population; and most northern, western, eastern, and central Europeans have >90% in the “northern” population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the “southern” population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.

Background and Purpose— Cerebrolysin showed neuroprotective and neurotrophic properties in various preclinical models of ischemia and small clinical trials. The aim of this large double-blind, placebo-controlled randomized clinical trial was to test its efficacy and safety in patients with acute ischemic stroke. Methods— Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptoms onset to active treatment (30 mL Cerebrolysin daily) or placebo (saline solution) given as intravenous infusion for 10 days in addition to aspirin (100 mg daily). The patients were followed up to 90 days. The primary end point was the result of a combined global directional test of modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale. Adverse events were documented to assess safety. Results— A total of 1070 patients were enrolled in this study. Five hundred twenty-nine patients were assigned to Cerebrolysin and 541 to placebo. The confirmatory end point showed no significant difference between the treatment groups. When stratified by severity however, a post hoc analysis of National Institutes of Health Stroke Scale and modified Rankin Scale showed a trend in favor of Cerebrolysin in patients with National Institutes of Health Stroke Scale >12 (National Institutes of Health Stroke Scale: OR, 1.27; CI lower bound, 0.97; modified Rankin Scale: OR, 1.27; CI lower bound, 0.90). In this subgroup, the cumulative mortality by 90 days was 20.2% in the placebo and 10.5% in the Cerebrolysin group (hazard ratio, 1.9661; CI lower bound, 1.0013). Conclusions— In this study, the confirmatory end point showed neutral results between the treatment groups. However, a favorable outcome trend was seen in the severely affected patients with ischemic stroke treated with Cerebrolysin. This observation should be confirmed by a further clinical trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00868283.