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

Orphanet J Rare Dis. 2018 Jun 25;13(1):100. doi: 10.1186/s13023-018-0842-2.


Background: Vascular 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.

Methods: We conducted a retrospective analysis of a monocentric vEDS cohort along with a literature review regarding sCCF in this condition.

Results: Of 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.

Conclusions: In 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.

Keywords: Carotid-cavernous fistula; Genetics; Neurology; Neuroophthalmology; Pathophysiology; Rare vascular disease; Vascular Ehlers-Danlos syndrome.

Publication types

  • Review

MeSH terms

  • Carotid-Cavernous Sinus Fistula / pathology
  • Carotid-Cavernous Sinus Fistula / physiopathology*
  • Cavernous Sinus / pathology
  • Cavernous Sinus / physiopathology
  • Ehlers-Danlos Syndrome / pathology
  • Ehlers-Danlos Syndrome / physiopathology*
  • Humans
  • Retrospective Studies