Basilar Artery Tortuosity Is Associated With White Matter Hyperintensities by TIMP-1

Arterial tortuosity is described as a common and distinctive feature of Loeys-Dietz syndrome (LDS), yet reports on arterial tortuosity are based on qualitative observations and none have investigated an association between tortuosity and cardiovascular outcomes in LDS or other connective tissue disorders. We performed a retrospective analysis of 90 patients ≤50 years of age with Marfan syndrome, LDS, Ehlers-Danlos syndrome, or nonspecific connective tissue disorder who underwent thoracic contrast-enhanced magnetic resonance angiography. Controls (n=30) underwent magnetic resonance imaging to exclude arrhythmogenic right ventricular dysplasia. Using a volume-rendered angiogram, vertebral arteries were measured along the curvature of the vessel (actual length) and linearly (straight length), and distance factor was calculated: [(actual/straight length-1)×100]. Each subject's maximum distance factor was designated the Vertebral Tortuosity Index (VTI). The VTI was compared among diagnostic groups and among patients with cardiac surgery, dissection, and death. Median age at magnetic resonance imaging was 19.6 years (range 0.2 to 50.1). VTI interrater reliability was excellent (intraclass correlation coefficient =0.987). The VTI was higher in Marfan syndrome (n=57, median 26; interquartile range 10 to 49) and LDS (n=13, median 58; interquartile range 18 to 92) compared with controls (median 4.5; interquartile range 3 to 6; P<0.001 for both). Higher VTI was associated with younger age at surgery even when controlling for root size (adjusted P=0.002). Vertebral tortuosity index ≥50 was associated with earlier age at dissection and death compared with VTI <50 (P=0.001 versus P<0.001). We found no difference in age at surgery, dissection, or death in Marfan syndrome compared with LDS. Arterial tortuosity measured by magnetic resonance angiography is a reproducible marker of adverse cardiovascular outcomes in connective tissue disorders.

There are only limited epidemiological studies evaluating the association between vertebrobasilar dolichoectasia (VBD) and outcomes. This study was designed to elucidate the outcome and prognosis of adults diagnosed with VBD by magnetic resonance angiography (MRA) and to ascertain if these outcomes were independent of known vascular risk factors. A cohort study was designed to compare VBD cases identified retrospectively from a computerised database of MRA reports with age and sex matched controls evaluated after a 4-7 year period, and 1440 MRA reports were reviewed. The inclusion criteria were age > or =18 years and a radiological diagnosis of VBD. Patients were excluded if there was haemodynamically significant stenosis or occlusion of the posterior circulation. Data were obtained by medical record review and telephone questionnaires. The primary outcome measure was transient or fixed posterior circulation dysfunction (PCD), with a secondary outcome measure of all cause mortality. Sixty four VBD cases were obtained, and 19 cases (30%) were excluded due to refusal and/or insufficient follow up data. From the same computerised database, 45 controls were selected by consecutive sampling. The mean age at follow up was 73.4 years for VBD cases and 73.1 years for controls, with a median follow up period of 64 months. VBD was associated with fixed/transient PCD (p = 0.0001; estimated adjusted odds ratio (OR) of 20.6 and confidence interval (CI) of 4.4 to 95.3), and with all cause mortality (OR = 3.6 CI 1.3 to 10.3); (p = 0.018). VBD cases had 36% mortality, with 50% occurring within 34 months of the initial diagnosis. The VBD cumulative survival curve was statistically different from the controls (p = 0.012 by Mantel-Cox log rank test). This study suggests that VBD may be an independent risk factor for stroke. VBD cases had an increased likelihood for PCD, all cause mortality, and reduced cumulative survival independent of other vascular risk factors in this cohort. Larger population based prospective studies are required to verify these results.

Dolichoectasia is an arterial disease that causes dilatation and/or tortuosity of the affected vessel. The prevalence of dolichoectasia increases with age, and this disease is also associated with other traditional cardiovascular risk factors. Multiple pathophysiological processes might lead to the development of dolichoectatic vessels, and activation of metalloproteinases and irregular turbulent blood flow seem to cause irreversible disruption of the internal elastic lamina. Intracranial dolichoectasia commonly presents with ischemic or hemorrhagic stroke, and/or cranial neuropathies. The posterior circulation is more frequently affected by the dolichoectatic process than the anterior circulation. A positive diagnosis of dolichoectasia requires visual assessment of vessel shape and, if the posterior circulation is affected, application of Smoker's criteria. Reproducible criteria that aid diagnosis of dolichoectasia in the anterior circulation are lacking. No specific treatment for dolichoectasia exists, and the surgical and medical therapies that have been used to treat this condition have not been systematically evaluated. More evidence is needed to better understand the underlying dilatatory artheriopathy that causes this disease, and to determine whether patients with dolichoectasia might benefit from early diagnosis. In this article, we provide a comprehensive review of current knowledge regarding dolichoectasia, and highlight gaps in our knowledge to aid future research.