Background and Purpose-It has been recently reported that a G3 A transition at nucleotide position 20210 in the 3Ј-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of deep venous thrombosis. To date, it is unknown whether this polymorphism also represents a risk factor for cerebral venous thrombosis (CVT). Methods-Venous blood samples were collected from 45 patients with CVT and from 354 healthy blood donors as controls. A second control group consisted of 131 subjects with acute ischemic stroke or transient ischemic attack (TIA). Genomic DNA was isolated from peripheral blood leukocytes. Amplification of DNA was performed by polymerase chain reaction (PCR). The G3 A transition at nucleotide position 20210 of the prothrombin gene was detected by allele-specific restriction digestion. Results-The G 20210 3 A transition in the prothrombin gene was found in a heterozygous form in 4 of 45 patients with CVT (8.9%) and in 8 of 354 healthy control subjects (2.3%). This difference was statistically significant (Pϭ0.010). The G 20210 3 A transition increased the relative risk for CVT approximately 5-fold (age-adjusted odds ratio 5.7; 95% CI 1.5 to 21.5). In contrast, in the group of patients with acute cerebral ischemia, only 3 of 131 subjects (2.3%) were heterozygous for the G 20210 3 A transition, which corresponded to the prevalence in the group of healthy blood donors. Conclusions-The recently described G 20210 3 A transition in the 3Ј-untranslated region of the prothrombin gene is an inherited risk factor for CVT but obviously not for acute ischemic stroke or TIA. (Stroke. 1998;29:1765-1769.)

In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.

Background: Paradoxical embolism via persistent foramen ovale (PFO) is suspected to be a frequent cause of stroke in younger patients. We investigated whether the prevalence of the risk factors for venous thrombosis factor V Leiden (FVL) and prothrombin G20210A mutation (PT G20210A) is increased in this group of patients. Methods: We examined FVL and PT G20210A mutation in 220 patients (group 1) with cerebral ischemia associated with a PFO and without other etiology, in 196 patients with cerebral ischemia of an etiology other than PFO (group 2), and in 362 healthy subjects (group 3) from the same region in Germany. Results: Heterozygosity for the PT G20210A mutation was more common in group 1 (5.0%) than in group 3 (1.4%; sex- and age-adjusted odds ratio 3.66; 95% CI 1.25–10.75; p = 0.01). By contrast, the mutation was not more common in group 2 (2.6%; odds ratio 1.50; 95% CI 0.42–5.41; p = 0.5). Prevalences of FVL were not different between groups. Conclusions: We identified PT G20210A but not FVL – the strongest genetic risk factor for deep venous thrombosis – to be significantly associated with stroke attributed to PFO. These findings rise doubts about the concept of paradoxical brain embolism as the dominating mechanism in stroke associated with PFO.

At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.