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their rupture may lead to CCF formation, SAH, or ICH Carotid-cavernous fistula Carotid-cavernous fistula typically occurs spontaneously or following head trauma (Jindal, 2005) carotid-cavernous fistula (CCF) most CCFs are direct and result from the rupture of the ICA into the cavernous sinus the bilateral lesion is not uncommon CCF can be visualized by noninvasive vascular imaging, such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA) therapy: embolization, balloon occlusion Systemic symptoms Systemic symptoms hyperelastic, soft skin affected individuals tend to bruise easily, and abnormal scarring may occur (specific cigarette paper scars) loose skin wrinkles hypermobile joints the loose joints are unstable and prone to dislocation and pain increased vascular fragility may result in bleeding (internal or external) the cardiac-valvular type specifically affects the heart valves kyphoscoliosis (kyphoscoliotic type) spondylodysplastic type features skeletal abnormalities such as abnormally curved limbs Diagnostic evaluation typical clinical presentation of arterial dissections or ruptures at a young age positive family history genetic testing gold standard the panel should include at least the and COL3A1, COL5A1 , COL5A2, COL1A1 , COL1A2 genes Comprehensive EDS panel if genetic testing is unavailable, electron microscopy (EM) findings can support the clinical diagnosis (Sevenich, 1980) abnormalities in collagen fibril architecture irregular fibril diameter, disorganized arrangement, or abnormal interfibrillar spacing vascular imaging preferably CTA, MRA major criteria generalized joint hypermobility (GJH) skin hyperextensibility and atrophic scarring minor criteria easy bruising soft, doughy skin skin fragility (or traumatic splitting) molluscoid pseudotumors subcutaneous spheroids hernia (or history thereof) epicanthal folds complications of joint hypermobility (e.g., sprains, luxation/subluxation, pain, flexible flatfoot) family history of a first-degree relative meeting clinical criteria Minimal criteria suggestive of cEDS: skin hyperextensibility and atrophic scarring + generalized joint hypermobility (GJH) and/or at least 3 minor criteria Management acute stroke therapy standard stroke protocols and IVT contraindications apply

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