title: Aberrations of dermal connective tissue in patients with cervical artery dissection (sCAD).
abstract: Spontaneous cervical artery dissection (sCAD) is a common cause of stroke in patients below 55 years of age. Hereditary connective tissue disorders, including Ehlers-Danlos syndrome type IV, have been associated with sCAD and suprastructural abnormalities of both collagen fibrils and elastic fibers have been found by transmission electron microscopy in the dermis of about 50% of sCAD patients. Here, we investigated dermal connective tissue abnormalities using a novel method. Transmission and immunogold electron microscopy were used to study mechanically generated fragments of dermal matrix suprastructures, in particular collagen fibrils. Analysis of dermal tissue of sCAD patients revealed structurally abnormal collagen fibrils with irregularly contoured surfaces and increased diameters, often associated with a faint or absent banding pattern. Interestingly, only a small number of fibrils displayed short abnormal sections along the length of the fibril. Collagens I and III were present in normal as well as abnormal sections of the fibrils.However, immunogold labeling for the two proteins was strongly increased in abnormal sections.A systematic blinded investigation of skin biopsies of 31 sCAD patients and 17 controls revealed abnormal collagen fibrils in 7 sCAD patients but none of the controls. We conclude that approximately 20% of sCAD patients show collagen fibril alterations, establishing a promising basis for further investigation of connective tissue aberrations in skin biopsies of sCAD patients.
authors.affiliation: Institut für Physiologische Chemie und Pathobiochemie, Universitätsklinikum Münster, 48129, Münster, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Uhlig
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
authors.forename: Ralf
authors.initials: R
authors.lastname: Dittrich
authors.forename: E Bernd
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
mesh_terms: D000328:Adult; D002536:Cerebral Arteries / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003238:Connective Tissue / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009210:Myofibrils / Q000473:pathology; D012867:Skin / Q000473:pathology*; D014020:Tissue Extracts / Q000737:chemistry
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D014020:Tissue Extracts