Pathophysiology of carotid-cavernous fistulas in vascular Ehlers-Danlos syndrome: a retrospective cohort and comprehensive review

Abstract

BackgroundVascular Ehlers-Danlos syndrome (vEDS) is a rare condition characterized by connective tissue fragility. Direct spontaneous carotid-cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted this study to understand the possible mechanisms of occurrence of sCCF in this subset of patients.MethodsWe conducted a retrospective analysis of a monocentric vEDS cohort along with a literature review regarding sCCF in this condition.ResultsOf 133 patients regularly followed in our centre between 2000 and 2017, 13 (9.8%) had a diagnosis of direct sCCF (92.3% female, median age 33.0 years, interquartile range (IQR) [26.0–39.5]). There were 7 Glycine missense and 6 splice-site variants but no variant leading to haploinsufficiency. The literature search identified 97 vEDS patients with direct sCCF (79.4% female, 7.2% sex not reported, median age 31.0 years, IQR [24.0–39.0]). Increased carotid circumferential wall stress, higher carotid distensibility and lower carotid intima-media thickness could contribute to a higher risk for direct sCCF in vEDS. There is no predictive factor for the occurrence of sCCF apart from female sex in vEDS.ConclusionsIn vEDS, anatomical and pathophysiological features of the intra-cavernous internal carotid artery make it prone to shunting in the cavernous sinus, due either to a spontaneous rupture or to a spontaneous dissection with pseudoaneurysm formation. Direct sCCF in seemingly healthy young individuals should be highly suggestive of vEDS and prompt further investigation.

Application of the 2017 criteria for vascular Ehlers‐Danlos syndrome in 50 patients ascertained according to the Villefranche nosology

“…Of note, in the new nosology, sCCF is considered a major criterion. In our cohort, sCCF was found in 9.5% of patients, in line with a recent study reporting a similar frequency (9.8%) in a cohort of 133 molecularly proven vEDS patients, emphasizing that sCCF, although rare, is highly characteristic of vEDS.…”

Endovascular Management of Direct Carotid–Cavernous Fistula: Evolution of Cost Effective Sandwich Technique

“…Overall, 0.2 to 0.3% of cases of craniofacial trauma present as direct CCF clinically. 2 3 4 5 6 In our study, a history of significant head injury (road traffic accidents, penetrating trauma from gun-shot injury, and fall from height) was present in the majority (~89%) of cases. Demographically the most vulnerable group is young male adults and this fact is also reflected in our study with a lower mean age (27.17 years) for male patients.…”

“… 2 3 4 5 In Ehlers–Danlos syndrome, intracranial arteries have type-3 collagen defects and decreased elastic tissue in the vessel wall. 6 In these cases, the inherent weakness of arterial wall media makes them prone to develop CCF spontaneously or after trivial trauma. This also creates a challenge for the interventionist to treat these patients, as they are more prone to develop intra- or postprocedure complications in the form of puncture site hematoma, arterial dissection, pseudoaneurysm formation, and even arterial perforation during the procedure.…”

“…Also, conversion of the procedure to parent artery occlusion was more in patients where we used detachable balloons as the primary embolizing material, as the behavior of balloons were unpredictable in several cases. 2 3 6 In 8 out of 21 cases (38.09%) where we used a detachable balloon as primary embolizing material, finally we had to go for parent artery occlusion to completely treat residual disease. Our results with detachable balloons were not as great as reported in the literature.…”

Ehlers-Danlos Syndrome: Immunologic contrasts and connective tissue comparisons

“…Due to anatomical and pathophysiological attributes, certain blood vessels are more prone to arterial complications which can further lead to spontaneous hemorrhage. For example, the hepatic arteries, renal arteries, splenic arteries, and internal carotid arteries are most commonly associated with arterial aneurysms [ 6 , 13 , 14 ]. Varicose veins can also be associated with vascular EDS [ 15 ].…”