Increased cervical vessel tortuosity in Loeys-Dietz Syndrome is not associated with intracranial aneurysms

Structured Abstract Background Loeys-Dietz Syndrome (LDS) is a heritable connective tissue disorder characterized by widespread arterial tortuosity and aneurysmal disease. Although intracranial aneurysms occur frequently in LDS, it is unclear whether cervical arterial tortuosity is associated with intracranial aneurysm risk. Methods We retrospectively reviewed patients with genetically confirmed LDS who underwent cervical and cerebrovascular imaging at our institution. Cervical carotid and vertebral tortuosities were derived from baseline CTA or MRA three-dimensional centerline reconstructions. Quantitative metrics such as total absolute curvature, peak curvature, number of curves, and inter-vessel asymmetry were compared between LDS and controls and between LDS subgroups based on the presence and multiplicity of intracranial aneurysms. Results Sixty-three LDS patients (17 TGFBR1 , 19 TGFB2 , 11 SMAD3 , 11 TGFB2 , 5 TGFB3 ) and 50 controls were analyzed. LDS patients had significantly greater carotid and vertebral tortuosity across all metrics compared to controls (p<0.001). Tortuosity varied by genotype, with highest values of carotid (p=0.0001) and vertebral tortuosity (p<0.0001) in TGFBR2 variants. Intracranial aneurysms were identified in 16 (25%) LDS patients. No direct association was observed between absolute carotid or vertebral tortuosity and intracranial aneurysm presence in LDS. In exploratory analyses, we observed a non-significant positive association between carotid asymmetry and multiple intracranial aneurysms (adjusted OR 3.2 95% CI, 0.7 to 14.0; p=0.126). Conclusions Cervical arterial tortuosity is a robust imaging feature of LDS but does not independently predict intracranial aneurysm presence. These findings support continued baseline cerebrovascular imaging and periodic surveillance in all LDS patients, independent of tortuosity burden.