Pathogenesis of cervical artery dissections - Association with connective tissue abnormalities

Background: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been p ostulated. Objective: To further assess the association of GAD with ultrast ructural abnormalities of the dermal connective tissue. Methods: In a multi center study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron m icroscopy. Results: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were s een in 36 of 65 patients (55%), consisting of the regular occurrence of com posite fibrils within collagen bundles that in some cases resembled the abe rrations found in Ehlers-Danlos syndrome type II or III and elastic fiber a bnormalities with minicalcifications and fragmentation. A grading scale acc ording to the severity of the findings is introduced. Intraindividual varia bility over time was excluded by a second biopsy of the skin in eight patie nts with pronounced aberrations. Recurrent CAD correlated with connective t issue aberrations. In addition, similar connective tissue abnormalities wer e detected in four first-degree relatives with familial GAD. Conclusion: CA D is associated with ultrastructural connective tissue abnormalities, mostl y without other clinical manifestations of a connective tissue disease. A s tructural defect in the extracellular matrix of the arterial wall leading t o a genetic predisposition is suggested. The dermal connective tissue abnor malities detected can serve as a phenotypic marker for further genetic stud ies in patients with CAD and large families to possibly identify the underl ying basic molecular defect(s).