Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

Background and Purpose-Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment. Methods-To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (Ͻ24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA). 6.7, PϽ0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism. Conclusions-Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention. Results-Of

Background and Purpose-The risk of recurrent stroke is highest within the first few weeks after a transient ischemic attack (TIA), and it is likely to be related to the underlying pathology. We sought to study the early risk of recurrent stroke by etiologic subtype. Methods-We prospectively studied 388 TIA patients. The cause of TIA was classified according to the Trial of ORG 10172 criteria: large-artery atherosclerosis (LAA, nϭ90), cardioembolism (nϭ87), small-vessel disease (nϭ68), undetermined (nϭ127), and other determined cause (nϭ16). Patients were followed up at 3 months. Risk factors and clinical symptoms for each subtype were recorded. Results-The duration of symptoms and clinical symptoms varied significantly among the different subtypes. LAA was associated with recurrent short episodes of weakness, whereas speech impairment and cortical symptoms were associated with cardioembolism (PϽ0.05).