CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

No abstract

This study describes the technical handling and the diagnostic evaluation of skin biopsies in order to standardize the assessment of the delicate morphologic abnormalities that are found in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from 126 patients with sCAD and from 29 healthy relatives were analyzed. The morphology of the connective tissue was normal in 54 patients with sCAD (43%) and aberrant in 72 patients with sCAD (57%). These latter patients were classified into three groups: in 43 patients, we repeatedly observed composite collagen fibrils and elastic fibers with fragmentation and minicalcifications. In 13 further patients, the dermis was significantly thinner than in healthy subjects. The collagen fibers contained fibrils with highly variable diameters. In a third group of 16 sCAD patients, the abnormalities were restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. The finding of different morphologic classes of aberrations among patients suggests that the connective tissue defects are genetically heterogeneous. The segregation of the connective tissue phenotype in three families suggested an autosomal dominant pattern of inheritance.

No abstract

Individual adjustment of the PVAB significantly reduces the incidence of inappropriate mode switch due to FFS.

Background and Purpose-The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (COL5A1) as a candidate gene for sCAD. Methods-We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction-amplified fragments of the whole COL5A1 coding sequence. Results-We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular COL5A1 sequences with some silent polymorphisms. Conclusions-Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD. (Stroke.1999;30:1887-1890.)Key Words: connective tissue disorders Ⅲ dissection Ⅲ genetics Ⅲ mutation S pontaneous cervical artery dissections (sCAD) are increasingly recognized as a cause of stroke among young and middle-aged patients. 1 A predisposing arteriopathy in these patients has been postulated. 2 A recent study by Brandt et al 3 substantiated the hypothesis of a predisposing defect in the extracellular matrix. These authors found ultrastructural abnormalities in skin biopsies of a majority of patients with sCAD and suggested an association with a connective tissue disorder. Major findings included numerous enlarged and irregular collagen fibrils and pronounced elastic fiber fragmentation. The abnormalities resembled the morphological alterations in patients with Ehlers-Danlos syndrome type II or III (EDS II/III). 4 Those changes were not observed in age-matched stroke patients with alternative etiologies of cerebral ischemic infarcts or in healthy control subjects. None of the patients with sCAD had other phenotypic manifestations of a known hereditary connective tissue disorder.Type V collagen belongs to the family of fibrillar collagens. [5][6][7] It is expressed at a low level in many tissues and plays an important role in type I fibrillogenesis by modulating and influencing fibril diameter. 8 -9 Mutations in COL5A1 and COL5A2 may lead to ultrastructural abnormalities similar to those observed in sCAD patients. 10 Furthermore, some patients with EDS I/II carry mutations in the COL5A1or the COL5A2 gene (for reference, see Michalickova et al 11 ). The ultrastructural similarities of dermal connective tissue aberrations of EDS II patients and sCAD patients prompted us to start this study and to analyze the full coding sequence of COL5A1 in patients with sCAD. Subjects and MethodsWe investig...

Skin biopsies from a patient with a dissection of the left internal carotid artery and from four of his children were analyzed by electron microscopy. The index patient and three children showed mild but regular electron microscopic connective tissue aberrations. They were considered as carriers of an unknown autosomal dominant mutation. Thirty-four candidate genes involved in the biosynthesis of the extracellular matrix were excluded by genetic linkage analysis as possible sites of a disease-causing mutation in this family (logarithm of odds [LOD]-score less than -2.0).

Workload-indexed blood pressure response (wiBPR) to exercise has been shown to be superior to peak systolic blood pressure (SBP) in predicting mortality in healthy men. Thus far, however, markers of wiBPR have not been evaluated for athletes and the association with vascular function is unclear. We examined 95 male professional athletes (26±5 y) and 30 male controls (26±4 y). We assessed vascular functional parameters at rest and wiBPR with a graded bicycle ergometer test and compared values for athletes with those of controls. Athletes had a lower pulse wave velocity (6.4±0.9 vs. 7.2±1.5 m/s, p=0.001) compared to controls. SBP/Watt slope (0.34±0.13 vs. 0.44±0.12 mmHg/W), SBP/MET slope (6.2±1.8 vs. 7.85±1.8 mmHg/MET) and peak SBP/Watt ratio (0.61±0.12 vs. 0.95±0.17 mmHg/W) were lower in athletes than in controls (p<0.001). The SBP/Watt and SBP/MET slope in athletes were comparable to the reference values, whereas the peak SBP/Watt-ratio was lower. All vascular functional parameters measured were not significantly correlated to the wiBPR in either athletes or controls. In conclusion, our findings indicate the potential use of the SBP/Watt and SBP/MET slope in pre-participation screening of athletes. Further, vascular functional parameters, measured at rest, were unrelated to the wiBPR in athletes and controls.