Evaluation of the obesity genes FTO and MC4R and the type 2 diabetes mellitus gene TCF7L2 for contribution to stroke risk: The Mannheim-Heidelberg Stroke Study.

OBJECTIVE: Studies evaluating genetic markers for vascular risk and risk of stroke are limited, and none of them evaluated obesity genes. The objective was to investigate the genetic markers related to obesity genes FTO and MC4R and the gene of type 2 diabetes mellitus TCF7L2 for their contribution to risk of stroke and transient ischemic attacks (TIA). METHODS: We recruited 379 consecutive patients with stroke/TIA and 379 healthy population-based controls. The single-nucleotide polymorphisms (SNPs) rs9937053 (FTO), rs2229616 (MC4R V103I), rs17782313 (188kb downstream of MC4R), and rs7903146 (TCF7L2) were evaluated for association with stroke using logistic regression analyses. RESULTS: The odds ratios for stroke/TIA were 1.14 (95%CI 0.91-1.42) for rs9937053/FTO, 1.11 (95%CI 0.49-2.51) for rs2229616/MC4R, 1.05 (95%CI 0.82-1.3) for rs17782313/MC4R, and 0.99 (95%CI 0.78-1.25) for rs7903146/TCF7L2. Further exploration revealed that male patients with the T allele of rs7903146/TCF7L2 had a worse clinical outcome compared with male patients carrying the C allele. CONCLUSION: The observed trends of obesity risk alleles for risk of stroke/TIA as well as the possible sex-specific differences in clinical outcomes found for the TCF7L2 (rs7903146) require replication in future studies. Our study demonstrates that candidate gene studies for common stroke may benefit from focusing on polymorphisms that predispose to vascular risk.

Contribution of obesity and abdominal fat mass to risk of stroke and transient ischemic attacks.

BACKGROUND AND PURPOSE: Waist circumference has been shown to be a better predictor of cardiovascular risk than body mass index (BMI). Our case-control study aimed to evaluate the contribution of obesity and abdominal fat mass to the risk of stroke and transient ischemic attacks (TIA). METHODS: We recruited 1137 participants: 379 cases with stroke/TIA and 758 regional controls matched for age and sex. Associations between different markers of obesity (BMI, waist-to-hip ratio, waist circumference and waist-to-stature ratio) and risk of stroke/TIA were assessed by using conditional logistic regression adjusted for other risk factors. RESULTS: BMI showed a positive association with cerebrovascular risk which became nonsignificant after adjustment for physical inactivity, smoking, hypertension, and diabetes (odds ratio 1.18; 95% CI, 0.77 to 1.79, top tertile versus bottom tertile). Markers of abdominal adiposity were strongly associated with the risk of stroke/TIA. For the waist-to-hip ratio, adjusted odds ratios for every successive tertile were greater than that of the previous one (2nd tertile: 2.78, 1.57 to 4.91; 3rd tertile: 7.69, 4.53 to 13.03). Significant associations with the risk of stroke/TIA were also found for waist circumference and waist-to-stature ratio (odds ratio 4.25, 2.65 to 6.84 and odds ratio 4.67, 2.82 to 7.73, top versus bottom tertile after risk adjustment, respectively). CONCLUSIONS: Markers of abdominal adiposity showed a graded and significant association with risk of stroke/TIA, independent of other vascular risk factors. Waist circumference and related ratios can better predict cerebrovascular events than BMI.

Early spontaneous recanalization following acute carotid occlusion.

BACKGROUND AND PURPOSE: Occlusion of the internal carotid artery (ICA) and stroke may be the consequence of either local thrombosis due to atherosclerosis or massive embolism. Up to date, there are only few reports of subsequent recanalization. METHODS: We report 12/76 cases of acute ICA occlusion leading to ischemic stroke, in which early recanalization was identified. Ultrasound and stroke MRI findings, therapeutic options, and outcome are described. RESULTS: 10/12 patients showed an- or hypoechogenic morphology of occlusion. While in 7/12 cases complete recanalization was seen, in 5/12 patients partial recanalization with filiform flow (4) or residual high-grade stenosis (1) was detected. 10/12 patients had territorial or subcortical infarction, while two showed small cortical lesions only. In 7/12 cases, a potential cardiac source of embolism was found. Five patients received tPA; four patients underwent early carotid endarterectomy of the partially recanalized ICA within 48 hours. In the 10-day follow-up examination 10/12 patients showed clinical improvement as measured by the NIHSS. CONCLUSIONS: Spontaneous recanalization after occlusion of the ICA may occur and might be more frequent than hitherto assumed. Echogenicity analysis and serial examinations of symptomatic ICA occlusion is useful for identifying a patient subgroup that might benefit from further therapy.

Vascular diagnosis and acute stroke: what, when and why not?

Even within the 3-hour time window, the less the delay to thrombolysis, the more likely it is to be effective. Delays caused by unnecessary examinations based on physicians' uncertainty about the relevance of vascular diagnostics must be overcome if acute therapy is to be administered efficiently. Only defined information concerning inclusion and exclusion criteria, a CT or preferably an MRI of the brain and limited additional data should be achieved prior to treatment and as quickly as possible, preferably within 1 h. All other information is to be gathered after the start of treatment, to assess the possible etiology of stroke, to classify the prognosis, and to recognize the possible need for early intervention such as in carotid stenosis. A primary diagnostic approach with MRI-guided treatment decision should be limited to cases with uncertain or 3- to 9-hour time window to improve selection of patients potentially at benefit from specific treatment and stroke unit/ICU care.

Multiparametric MRI and ultrasound findings in patients with internal carotid artery dissection.

In this study, clinical, MRI, and ultrasound findings in 33 patients with 37 MRI-confirmed internal carotid artery dissections (ICADs) were investigated. In 24 of 37 (64.9%) diffusion-weighted MRI (DWI) revealed acute ischemic brain lesions. ICADs with subsequent DWI lesions usually had a concentric position of the mural hematoma (14 of 24; 58.3%). In contrast, ICADs without DWI lesions (13 of 37; 35.1%) demonstrated an eccentric position of the mural hematoma (10 of 13; 76.9%), sometimes without ultrasound abnormality (5 of 13; 38.5%), while nonischemic clinical signs were frequent (11 of 13; 84.6%). A hemodynamic stroke pattern with comparatively large ischemic lesions along the hemodynamic risk zones was noted in 7 of 24 patients (29.2%).

Hemodynamic reserve and high-intensity transient signals in moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) as a rare obstructive cerebrovascular disease is assumed to present with ischemic symptoms due to hemodynamic compromise. However, alternative mechanisms, such as cerebral embolism in low-flow territories, may also contribute to clinical symptoms. The incidence of high-intensity transient signals (HITS) and the degree of hemodynamic compromise were studied in symptomatic patients with MMD. METHODS: Twenty-four patients (17 female, 7 male; mean age 33 +/- 13 years) with clinical symptoms attributable to cerebral ischemia and the angiographic features of MMD (21 definite form, 3 probable MMD; 22 patients 'late stage' MMD, 2 patients 'early stage' MMD) in 45 affected hemispheres were enrolled in the present study. Patients underwent parallel estimation of hemodynamic compromise by means of functional blood flow (rCBF) studies using SPECT, PET or xenon-CT and HITS detection by TCD. RESULTS: Hemodynamic compromise was observed in 37/40 (92%) hemispheres studied. During TCD monitoring, HITS were detected in 3 patients (12.5%), with a total frequency of 3 (6.6%) in the 45 hemispheres investigated. All patients with HITS showed hemodynamic compromise in functional rCBF studies. In these patients, HITS were recorded ipsilateral to the symptomatic hemisphere. HITS occurred in late stage MMD patients only once, while both cases with early stage MMD demonstrated multiple HITS. CONCLUSIONS: The incidence of HITS in patients with MMD appears to be lower compared to patients with atherosclerotic or atherothrombotic arterial obstructions. In addition, ischemia-related symptoms in 'late stage' MMD seem to be caused by hemodynamic compromise in the majority of these patients.