However, ultrastructural abnormalities of the dermal connective tissue components are discernible in two out of three patients with spontaneous dissection. Ehlers–Danlos syndrome type 4, caused by mutations of the COL3A gene, leads to defective production of the collagen, type III, alpha 1 protein and causes skin fragility as well as weakness of the walls of arteries and internal organs. Marfan syndrome results from mutations in the FBN1 gene, defective production of the protein fibrillin-1, and a number of physical abnormalities including aneurysm of the aortic root.There have also been reports in other genetic conditions, such as osteogenesis imperfecta type 1, autosomal dominant polycystic kidney disease and pseudoxanthoma elasticum, α1 antitrypsin deficiency and hereditary hemochromatosis, but evidence for these associations is weaker. Genetic studies in other connective tissue-related genes have mostly yielded negative results. Other abnormalities to the blood vessels, such as fibromuscular dysplasia, have been reported in a proportion of cases. Atherosclerosis does not appear to increase the risk.There have been numerous reports of associated risk factors for vertebral artery dissection; many of these reports suffer from methodological weaknesses, such as selection bias. Elevated homocysteine levels, often due to mutations in the MTHFR gene, appear to increase the risk of vertebral artery dissection. People with an aneurysm of the aortic root and people with a history of migraine may be predisposed to vertebral artery dissection. Vascular tortuosity or redundancy in young patients is associated with an increased risk of spontaneous dissection.
The vertebral artery supplies a number of vital structures in the posterior cranial fossa, such as the brainstem, the cerebellum and the occipital lobes. The brainstem harbors a number of vital functions (such as respiration) and controls the nerves of the face and neck. The cerebellum is part of the diffuse system that coordinates movement. Finally, the occipital lobes participate in the sense of vision.Dissection occurs when blood accumulates in the wall of the blood vessel. This is most likely due to a tear in the tunica intima (the inner layer), allowing blood to enter the tunica media, although other lines of evidence have suggested that the blood may instead arise from the vasa vasorum, the small blood vessels that supply the outer layer of larger blood vessels. Various theories exist as to whether people who sustain carotid and vertebral artery dissection, even if they do not have a connective tissue disorder, have an underlying vulnerability. Biopsy samples of skin and other arteries has indicated that this might be a possibility, but no genetic defect in collagen or elastin genes has been convincingly proven. Other studies have indicated inflammation of the blood vessels, as measured by highly sensitive C-reactive protein (hsCRP, a marker of inflammation) in the blood.Once dissection has occurred, two mechanisms contribute to the development of stroke symptoms. Firstly, the flow through the blood vessel may be disrupted due to the accumulation of blood under the vessel wall, leading to ischemia (insufficient blood supply).